TY - JOUR. T1 - Characterization of a radiolabeled small molecule targeting leukocyte function-associated antigen-1 expression in lymphoma and leukemia. AU - Poria, Rahul B.. AU - Norenberg, Jeffrey P.. AU - Anderson, Tamara L.. AU - Erion, Jack. AU - Wagner, Carston R.. AU - Arterburn, Jeffrey B.. AU - Larson, Richard S.. PY - 2006/11/20. Y1 - 2006/11/20. N2 - Objective: Leukocyte function-associated antigen-1 (LFA-1) is constitutively expressed on leukocytes, including overexpression on lymphomas and leukemias. We have developed a derivative of BIRT 377, an allosteric inhibitor of LFA-1, which may be chemically tagged without affecting binding. In this study, we modified this derivative, (R)-1-(4-aminobutyl)-5-(4-bromobenzyl) -3-(3,5-dichlorophenyl)-5-methylimidazolidine-2,4-dione (butylamino-NorBIRT), and demonstrated its potential as a noninvasive imaging agent. Methods: Specific binding of fluorescein-labeled butylamino-NorBIRT to both human and murine cells was demonstrated using ...

Signaling through the leukocyte function-associated antigen 1 (LFA-1) molecule has previously been shown to induce homotypic aggregation in T cells and to induce cytoskeletal changes in T lymphoma cells. In this study we describe the induction of a d

Integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide), also known as ITGAL, is a human gene which functions in the immune system. It is involved in cellular adhesion and costimulatory signaling. It is the target of the drug efalizumab. ITGAL encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling. CD11a is one of the two components, along with CD18, which form lymphocyte function-associated antigen-1. Efalizumab acts as an immunosuppressant by binding to CD11a but was ...

Integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide), also known as ITGAL, is a human gene which functions in the immune system. It is involved in cellular adhesion and costimulatory signaling. It is the target of the drug efalizumab.. ITGAL encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling.[1]. CD11a is one of the two components, along with CD18, which form lymphocyte function-associated antigen-1.. Efalizumab acts as an immunosuppressant by binding to ...

The I domain of lymphocyte function-associated antigen (LFA)-1 contains an intercellular adhesion molecule (ICAM)-1 and ICAM-3 binding site, but the relationship of this site to regulated adhesion is unknown. To study the adhesive properties of the LFA-1 I domain, we stably expressed a GPI-anchored form of this I domain (I-GPI) on the surface of baby hamster kidney cells. I-GPI cells bound soluble ICAM-1 (sICAM-1) with a low avidity and affinity. Flow cell experiments demonstrated a specific rolling interaction of I-GPI cells on bilayers containing purified full length ICAM-1 or ICAM-3. The LFA-1 activating antibody MEM-83, or its Fab fragment, decreased the rolling velocity of I-GPI cells on ICAM-1-containing membranes. In contrast, the interaction of I-GPI cells with ICAM-3 was blocked by MEM-83. Rolling of I-GPI cells was dependent on the presence of Mg2+. Mn2+ only partially substituted for Mg2+, giving rise to a small fraction of rolling cells and increased rolling velocity. This suggests that the

The effect of polyclonal (anti alpha and beta chain) and monoclonal (anti alpha-chain) antibodies against lymphocyte function-associated antigen 1 (LFA-1) on T cell activation was studied. When added at the beginning of activation but not after 24 h or later the antibodies as well as the F(ab)2 or Fab fragments of polyclonal antibodies inhibited concanavalin A (Con A)-induced proliferation, interleukin 2 (IL-2) production, and the expression of receptors for IL-2 and transferrin. The inhibitory effect reached a maximum at the same time as optimal proliferation (72 h). Inhibition of proliferation lasted for 5 days or longer, although IL-2 production was only inhibited during the first 48 h of culture. Receptors for IL-2 and transferrin were re-expressed to the original level after 3 days of activation. Addition of external IL-2 at the beginning of the anti-LFA-1 containing culture prevented the inhibition of IL-2 receptor expression, while inhibition of transferrin receptor expression was unaffected,

We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...

Inflammation is a defense response of the body to an event of injury or tissue damage. Leukocytes circulating in the bloodstream are stimulated by chemokines released by endothelial cells that enable them to adhere and transmigrate to the site of infection. Leukocyte extravasation from the blood vessels towards the site of inflammation is a sequential and overlapping process involving leukocyte rolling, adhesion and transendothelial migration. Adhesion is critical for T-cell trafficking and antigen recognition and is mediated in part by integrins, a large family of αβ heterodimeric cell surface proteins. The β2-integrin lymphocyte function-associated antigen-1 (LFA-1 /αLβ2) and the β1-integrin very late antigen-4 (VLA-4/α4β1) promote T cell interactions with their ligands intercellular and vascular cell adhesion molecules (ICAMs and VCAMs) respectively which are expressed on endothelial cells. VLA-4 and LFA-1 directly participate in cell arrest under flow, whereas firm adhesion is ...

We have expressed in Escherichia coli the two N-terminal immunoglobulin (Ig)-like domains of the intercellular adhesion molecule 1 (ICAM-1). The first 188 residues of ICAM-1 were expressed with an N-terminal methionine (MP188) or as a maltose-binding fusion protein which was cleaved with factor Xa (XP188). After refolding, both MP188 and XP188 were active in binding to the leukocyte integrin lymphocyte function-associated antigen 1, which has previously been shown to bind to the N-terminal Ig domain of ICAM-1. The major group of rhinoviruses and malaria-infected erythrocytes bind to distinct sites within the first Ig-like domain of ICAM-1. Both MP188 and XP188 bound to malaria-infected erythrocytes; however, only XP188 inhibited human rhinovirus plaque formation. A product (MdQ1P188) with the initiation methionine fused to residue 2, i.e., with glutamine 1 deleted, inhibited plaque formation. MdQ1P188 was able to induce a conformational change of the virus capsid as shown by conversion of 149S ...

Clone REA378 recognizes the human CD11a antigen, a single-pass type I membrane protein also known as integrin α-L (ITGAL). Integrins are heterodimeric adhesion molecules comprised of α- and β-subunits that participate in immune cell interactions as well as in immune cell-extracellular matrix interactions. CD11a combines with CD18 (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 is a receptor for CD54 (ICAM-1), CD102 (ICAM-2), CD50 (ICAM-3), and CD242 (ICAM-4). It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T cell-mediated killing, and antibody dependent killing by granulocytes and monocytes. Interactions between LFA-1 and CD54 (ICAM-1) play a critical role in T cell-B cell collaboration. Additional information: Clone REA378 displays negligible binding to Fc receptors. - Belgique

Clone REA378 recognizes the human CD11a antigen, a single-pass type I membrane protein also known as integrin α-L (ITGAL). Integrins are heterodimeric adhesion molecules comprised of α- and β-subunits that participate in immune cell interactions as well as in immune cell-extracellular matrix interactions. CD11a combines with CD18 (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 is a receptor for CD54 (ICAM-1), CD102 (ICAM-2), CD50 (ICAM-3), and CD242 (ICAM-4). It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T cell-mediated killing, and antibody dependent killing by granulocytes and monocytes. Interactions between LFA-1 and CD54 (ICAM-1) play a critical role in T cell-B cell collaboration. Additional information: Clone REA378 displays negligible binding to Fc receptors. - Danmark

Sigma-Aldrich offers abstracts and full-text articles by [G Liu, J T Link, Z Pei, E B Reilly, S Leitza, B Nguyen, K C Marsh, G F Okasinski, T W von Geldern, M Ormes, K Fowler, M Gallatin].

Lifitegrast is an integrin lymphocyte function-associated antigen-1 (LFA-1) antagonist; inhibits Jurkat T cell attachment to ICAM-1 with an IC50 of 2.98 nM. Buy Integrin inhibitor Lifitegrast from AbMole BioScience.

Abstract. We recently reported that cross-linking the leukocyte common antigen (CD45) can rapidly induce aggregation of human peripheral blood mononuclear cell

In theory, the interruption of leukocyte-leukocyte and leukocyte-endothelium interactions in acute myocardial infarction may be clinically salutary. Tanaka et al. [21]evaluated the effect of anti-CD18 monoclonal antibody infusion on myocardial neutrophil accumulation and infarct size in a dog model of ischemia and reperfusion. They found that neutrophil accumulation contributed to reduced postischemic microvascular perfusion, in keeping with the observation of Engler et al. [20]; however, anti-CD18 monoclonal antibody infusion did not affect infarct size in that model. In rabbits, in contrast, it was demonstrated that neutrophils do exacerbate tissue injury after a 30-min period of ischemia [22]. Infusion of an anti-CD18 monoclonal antibody before reperfusion resulted in a reduction of myocardial infarct size.. Acute myocardial infarction is a convenient model for the study of changes in leukocyte adhesion molecule expression secondary to ischemia and infarction because the magnitude of the ...

TY - JOUR. T1 - Interleukin-18/interferon-γ-inducing factor, a novel cytokine, up- regulates ICAM-1 (CD54) expression in KG-1 cells. AU - Kohka, Hideo. AU - Yoshino, Tadashi. AU - Iwagaki, Hiromi. AU - Sakuma, Isao. AU - Tanimoto, Tadao. AU - Matsuo, Yosinobu. AU - Kurimoto, Masashi. AU - Orita, Kunzo. AU - Akagi, Tadaatsu. AU - Tanaka, Noriaki. PY - 1998/10. Y1 - 1998/10. N2 - Intercellular adhesion molecule-1 (ICAM-1, CD54) is a membrane glycoprotein and a member of the immunoglobulin superfamily. It plays a central role in cell to cell-mediated immune responses and is a ligand for leukocyte function-associated antigen-1 (LFA-1). We report here that a newly discovered cytokine, interferon-γ-inducing factor (IGIF) [H. Okamura et al. (1995) Nature 378, 88] recently proposed to be designated as IL-18, selectively up-regulates ICAM-1 expression in KG-1 cells, a human myelomonocytic cell line, in which IL-18 also enhances interferon-γ production. IL-18 induced heterotypic aggregation between ...

T-lymphocyte migration is important for homing, cell trafficking, and immune surveillance. T-lymphocytes express lymphocyte function-associated antigen-1 (LFA-1; αLβ2) and very late antigen-4 (VLA-4; α4β1), which bind to their cognate ligands, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These adhesive interactions provide T-lymphocytes with the ability to withstand hemodynamic shear forces to facilitate adhesion and migration along the blood endothelium. Recently, it has been shown that T-lymphocytes will crawl upstream against the direction of flow on surfaces functionalized with ICAM-1. Here, we have investigated whether the identity of the receptor and the magnitude of its engagement affects the direction of T-lymphocyte migration under flow. We used microcontact printed ICAM-1 and VCAM-1 PDMS surfaces on which density and type of adhesion molecule can be tightly controlled and non-specific adhesion adequately blocked. Using a laminar flow chamber,

CD2 (cluster of differentiation 2) is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells. It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette receptor. It interacts with other adhesion molecules, such as lymphocyte function-associated antigen-3 (LFA-3/CD58) in humans, or CD48 in rodents, which are expressed on the surfaces of other cells. In addition to its adhesive properties, CD2 also acts as a co-stimulatory molecule on T and NK cells. CD2 is a specific marker for T cells and NK cells, and can therefore be used in immunohistochemistry to identify the presence of such cells in tissue sections. The great majority of T cell lymphomas and leukaemias also express CD2, making it possible to use the presence of the antigen to distinguish these conditions from B cell neoplasms. Due to its structural characteristics, CD2 is a member of the immunoglobulin superfamily; it possesses two immunoglobulin-like ...

Object. Leukocyte-endothelial cell interactions occurring in the first hours after subarachnoid hemorrhage (SAH) initiate changes in the endothelium and vessel wall that lead to an influx of leukocytes and the development of chronic vasospasm days later. Upregulation of intercellular adhesion molecule-1 (ICAM-1), also called CD54, appears to be a crucial step in this process. There is increasing experimental evidence that blocking the interaction between ICAM-1, which is expressed on endothelium, and integrins such as lymphocyte function-associated antigen-1 (CD11a/CD18) and macrophage antigen-1 (complement receptor 3, CD11b/CD18), which are expressed on the surface of leukocytes, prevents not only inflammation of vessel walls but also chronic vasospasm. The authors extend their previous work with monoclonal antibody (mAb) blockade of leukocyte migration to a nonhuman primate model of chronic, posthemorrhagic cerebral vasospasm.. Methods. Before surgery was performed, six young adult male ...

CD2, also known as T-cell surface antigen CD2, is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells. It interacts with other adhesion molecules, such as lymphocyte function-associated antigen-3 (LFA-3/CD58) in hum ...

CD2, also known as T-cell surface antigen CD2, is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells. It interacts with other adhesion molecules, such as lymphocyte function-associated antigen-3 (LFA-3/CD58) in hum ...

Lifitegrast is a non-steroidal, small molecule, integrin antagonist that inhibits lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18), which is being

SARcode Bioscience, Inc., founded in 2006, is a venture-backed ophthalmic biopharmaceutical company. SARcodes lead development program is a novel class of lymphocyte function-associated antigen-1 (LFA-1) antagonists for the treatment T-cell mediated inflammatory diseases.. ...

Transfusion-related alloimmunization is a potent barrier to the engraftment of allogeneic hematopoietic stem cells in patients with nonmalignant diseases (NMDs). Memory T cells, which drive alloimmunization, are relatively resistant to commonly used conditioning agents. Alefacept, a recombinant leukocyte function antigen-3/IgG1 fusion protein, targets CD2 and selectively depletes memory versus naive T cells. Three multiply transfused pediatric patients with NMD received a short course of high-dose i.v. alefacept (.25 mg/kg/dose on days −40 and −9 and .5 mg/kg/dose on days −33, −26, −19, and −12) before undergoing unrelated allogeneic transplant in the setting of reduced-intensity pretransplant conditioning and calcineurin inhibitor-based post-transplant graft-versus-host disease (GVHD) prophylaxis. Alefacept infusions were well tolerated in all patients. Peripheral blood flow cytometry was performed at baseline and during and after alefacept treatment. As expected, after the 5 weekly ...

Integrin alpha L beta 2 products available through Novus Biologicals. Browse our Integrin alpha L beta 2 product catalog backed by our Guarantee+.

transplant organs such as kidneys. They respond by recognising foreign antigens or peptides in the lymph nodes or sites of infection in the body. This leads to the proliferation of T cells and the expansion of reactive cells. The ability to respond depends on the movement of T-cells and length of time that T-cells spend attached to antigen presenting cells such as dendritic cells (DCs) that present the foreign antigen. Ligation of the antigen-receptor (also called the T-cell receptor or TCR) sends intracellular signals (termed the inside-out pathway) that slow T-cell motility allowing them to make stable contacts with DCs. Although essential for T cell function, the identity of the T cell receptor inside-out pathway for lymphocyte function-associated antigen 1 (LFA-1) adhesion has proved elusive.. As published this month in Immunity, the Rudd lab reports the identification of a novel inside-out pathway that is mediated by N-terminal SKAP1 (SKAP-55) domain binding to the C-terminal ...

Estradiol (E2) plays a key role in breast cancer progression. Most breast cancer recurrences express the estrogen receptor (ER), but nearly 50% of patients are resistant to anti-estrogen therapy. Novel therapeutic targets of ER positive breast cancers are needed. Protumoral neutrophils expressing the lymphocyte function-associated antigen 1 (LFA-1) integrin may mediate cancer metastasis and transforming growth factor β1 (TGFβ1) is the major chemoattractant for neutrophils. The role of E2 in neutrophil-ER+ breast cancer cell interactions is unknown. We studied this in vivo using murine breast cancers in immunocompetent mice and human breast cancers in nude mice. Cell dissemination was evaluated in a zebrafish model, and microdialysis of breast cancer patients was performed. In vitro studies were done with mammosphere cultures of breast cancer cells and human neutrophils. We found that E2 increased the number of LFA-1+ neutrophils recruited to the invasive edge of mouse tumors, increased TGFβ1 ...

Background CD2 interacts with lymphocyte function-associated antigen (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytoplasmic domain is...

This study aimed to determine the effects of dietary spermine supplementation on the inflammatory response and immune function of the thymus and spleen in piglets. Eighty suckling piglets were randomly assigned to receive adequate nutrients supplemented with spermine (0.4 mmol/kg body weight) or restricted nutrient intake supplemented with normal saline for 7 h or 3, 6 and 9 days in pairs. Regardless of treatment time, spermine supplementation decreased (p , 0.05, compared with the controls) the following: (1) tumour necrosis factor α (TNF-α), interleukin (IL)-1β, 2 and 6, and interferon (IFN)-γ levels in serum; (2) gene expression of cluster of differentiation 8 and integrin beta-2 in the thymus and spleen and the lymphocyte function-associated antigen 1 in the thymus; (3) mRNA levels of TNF-α, IL 1β, 2, 6, and 12, IFN-γ and inducible nitric oxide synthase in the thymus and spleen, as well as IL-8 in the spleen; and (4) eukaryotic IF4E-binding protein 1, Janus kinase 2, signal transducer ...

PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

购买LFA3小鼠单克隆抗体[MEM-63](ab26006)，LFA3抗体经Flow Cyt验证，可与人,猪样本反应。产品出库一年都在质保范围内。中国现货速达。

Despite continued reductions in short-term rejection rates, long-term outcomes have not significantly improved in the past decade. In the face of this the press...

Integrins are heterodimeric transmembrane proteins that play a fundamental role in the migration of leukocytes to sites of infection or injury. We found that protein tyrosine phosphatase nonreceptor type 22 (PTPN22) inhibits signaling by the integrin lymphocyte function-associated antigen-1 (LFA-1) in effector T cells. PTPN22 colocalized with its substrates at the leading edge of cells migrating on surfaces coated with the LFA-1 ligand intercellular adhesion molecule-1 (ICAM-1). Knockout or knockdown of PTPN22 or expression of the autoimmune disease-associated PTPN22-R620W variant resulted in the enhanced phosphorylation of signaling molecules downstream of integrins. Superresolution imaging revealed that PTPN22-R620 (wild-type PTPN22) was present as large clusters in unstimulated T cells and that these disaggregated upon stimulation of LFA-1, enabling increased association of PTPN22 with its binding partners at the leading edge. The failure of PTPN22-R620W molecules to be retained at the ...

TY - JOUR. T1 - Dependency on intercellular adhesion molecule recognition and local interleukin-2 provision in generation of an in vivo CD8+ T-cell immune response to murine myeloid leukemia. AU - Boyer, M. W.. AU - Orchard, P. J.. AU - Gorden, K. B.. AU - Anderson, P. M.. AU - McIvor, R. S.. AU - Blazar, B. R.. PY - 1995/5/1. Y1 - 1995/5/1. N2 - The immune response to a murine myeloid leukemia (cell line C1498) was studied in vitro and in vivo. Natural killer (NK) cells and CD8+ cytotoxic T lymphocytes (CTL) were shown to lyse C1498 in vitro through the binding of leukocyte function antigen-1 (LFA-1) on effectors and intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on C1498 target cells. However, the ability of nonimmunized mice to resist an in vivo challenge of a low dose (104) of C1498 was NK-cell, but not T-cell dependent. The failure of T cells to participate in the immune surveillance of a low leukemia burden appeared, in part, because of a lack of expansion of leukemia reactive CTL ...

PROSTVAC-V/F is a live attenuated viral vector-based investigational vaccine product that is comprised of two component viral vectors, to be used together in a prime-boost vaccination regimen: (1) PROSTVAC-V: Recombinant vaccinia virus that contains a modified gene encoding human prostate-specific antigen (PSA) and genes encoding three human immunological costimulatory molecules: B7.1, intracellular adhesion molecule-1 (ICAM-1), and leukocyte function-associated antigen-3 (LFA-3) (or TRIad of COstimulatory Molecules, TRICOM™); and (2) PROSTVAC-F: Recombinant fowlpox virus that co-expresses the same four human genes as PROSTVAC-V. ...

PROSTVAC-V/F is a live attenuated viral vector-based investigational vaccine product that is comprised of two component viral vectors, to be used together in a prime-boost vaccination regimen: (1) PROSTVAC-V: Recombinant vaccinia virus that contains a modified gene encoding human prostate-specific antigen (PSA) and genes encoding three human immunological costimulatory molecules: B7.1, intracellular adhesion molecule-1 (ICAM-1), and leukocyte function-associated antigen-3 (LFA-3) (or TRIad of COstimulatory Molecules, TRICOM™); and (2) PROSTVAC-F: Recombinant fowlpox virus that co-expresses the same four human genes as PROSTVAC-V ...

The recognition events that mediate adaptive cellular immunity and regulate antibody responses depend on intercellular contacts between T cells and antigen-presenting cells (APCs). T-cell signalling is initiated at these contacts when surface-expressed T-cell receptors (TCRs) recognize peptide fragments (antigens) of pathogens bound to major histocompatibility complex molecules (pMHC) on APCs. This, along with engagement of adhesion receptors, leads to the formation of a specialized junction between T cells and APCs, known as the immunological synapse, which mediates efficient delivery of effector molecules and intercellular signals across the synaptic cleft. T-cell recognition of pMHC and the adhesion ligand intercellular adhesion molecule-1 (ICAM-1) on supported planar bilayers recapitulates the domain organization of the immunological synapse, which is characterized by central accumulation of TCRs, adjacent to a secretory domain, both surrounded by an adhesive ring. Although accumulation of TCRs at

Intercellular adhesion molecule 1 (ICAM-1) is a 90 kd inducible surface glycoprotein that promotes adhesion in immunological and inflammatory reactions. ICAM-1 is a ligand of lymphocyte function-associated antigen-1 (LFA-1), an alpha beta complex that is a member of the integrin family of cell-cell and cell-matrix receptors. ICAM-1 is encoded by an inducible 3.3 kb mRNA. The amino acid sequence specifies an integral membrane protein with an extracellular domain of 453 residues containing five immunoglobulin-like domains. Highest homology is found with neural cell adhesion molecule (NCAM) and myelin-associated glycoprotein (MAG), which also contain five Ig-like domains. NCAM and MAG are nervous system adhesion molecules, but unlike ICAM-1, NCAM is homophilic. The ICAM-1 and LFA-1 interaction is heterophilic and unusual in that it is between members of the immunoglobulin and intergrin families. Unlike other integrin ligands, ICAM-1 does not contain an RGD sequence.

Large granular lymphocytes, mediators of NK activity, bind to other cells using both the LFA (lymphocyte function-associated)-1-ICAM and the CD2-LFA-3 adhesion pathways. Here we have studied the motility and ultrastructure of large granule lymphocyte (LGL) on lipid bilayers containing purified LFA-1, ICAM-1, and the transmembrane and glycophosphatidylinositol isoforms of LFA-3. LGLs moved at 8 microns/min on ICAM-1 but poorly (less than 1 microns/min) on its receptor pair LFA-1. TM-LFA-3 promoted locomotion at a rate close to ICAM-1, whereas the cells were less motile on GPI-LFA-3. The difference in the rates of locomotion on the two isoforms of LFA-3 is presumably attributable to their difference in anchoring and lateral mobility in the bilayer. In spite of the variation in motility the ultrastructure of the adhering cells was similar on all four ligands. LGLs contacted the membrane variably, i.e., cells adhering only in a few small areas or in larger areas were detected on each ligand. The ...

The primary objective of this study is to assess the safety and determine the recommended dose of AIC100 for phase II study in patients with relapsed/refractory poorly differentiated thyroid cancer and in patients with anaplastic thyroid cancer that are BRAF wild-type, or BRAF mutant anaplastic thyroid cancer after failure of BRAF-mutant specific therapy.. Upon enrollment, patients will undergo leukapheresis for collection of autologous lymphocytes. The autologous T cells will be transfected and expanded in-vitro to generate the AIC100 product. After lymphodepleting therapy, AIC100 will be infused.. The study drug, AIC100, consists of autologous CAR T cells containing the I domain of lymphocyte function-associated antigen-1 (LFA-1) and targeting its over-expressed physiological ligand, intercellular adhesion molecule-1 (ICAM-1) on thyroid cancer. AIC100 cells also express the transmembrane domain of CD8 alpha and intracellular domains of the co-stimulatory receptors CD28 and 41BB, and the ...

A monoclonal antibody targeting lymphocyte function-associated antigen 1 (LFA-1), a mediator of T cell adhesion, was introduced in 2006 and produced a potent anti-inflammatory effect, but cases of JC virus, which leads to the deadly brain infection PML, were soon observed in patients. The drug was removed from the market.. Dr. Mors lab looked at targeting just one of the two types of T cell adhesion rather than relying on global adhesion. Through a series of experiments, the researchers eventually focused on the phospholipase C epsilon 1 (PLC-e-1) gene. In the absence of this gene, they found, there was no activation of the Rap1 protein, a promoter of T cell adhesion.1 This effect was seen in only one type of adhesion.. Researchers have also found that, in animal models, arthritis scores were lower in the absence of PLC-e-1, suggesting that this enzyme is required for migration of T cells to the joint.. ...

CYTIP (cytohesin interacting protein) is an intracellular molecule induced in dendritic cells during maturation. CYTIP modulates the binding intensity of the adhesion molecule LFA-1. If dendritic cells are silenced for CYTIP they keep longer contacts with T-cells resulting in a lower T cell stimulation. We identified Suppressor of cytokine signaling-1 (SOCS-1) as a binding partner for CYTIP in human monocyte derived dendritic cells. In Western blot analyses we found that CYTIP expression is down regulated at later time points, starting at about 72 hours after induction of maturation. To investigate a possible role for SOCS-1 in taking CYTIP to the degradation machinery of the cell we measured endogenous CYTIP protein levels in mature dendritic cells transfected with SOCS-1 encoding plasmid in quantitative Western blot analyses. We observed lower amounts of endogenous CYTIP in mature dendritic cells transfected with SOCS-1 encoding plasmid compared with untransfected dendritic cells. Experiments with the

Asthma is a heterogeneous airway inflammatory disease characterized by increased airway hyperreactivity (AHR) to specific and unspecific stimuli. Group 2 innate lymphoid cells (ILC2)s are type-2 cytokine secreting cells capable of inducing eosinophilic lung inflammation and AHR independent of adaptive immunity. Remarkably, reports show that ILC2s are increased in the blood of human asthmatics as compared to healthy donors. Nevertheless, whether ILC2 expression of adhesion molecules regulates ILC2 trafficking remains unknown. Our results show that IL-33-activated ILC2s not only express LFA-1 but also strikingly LFA-1 ligand ICAM-1. Both LFA-1−/− and ICAM-1−/− mice developed attenuated AHR in response to IL-33 intranasal challenge, associated with a lower airway inflammation and less lung ILC2 accumulation compared to controls. Our mixed bone marrow chimera studies however revealed that ILC2 expression of LFA-1 - but not ICAM-1 - was required for their accumulation in the inflamed lungs.

Principal Investigator：WATANAVBE Hiroaki,渡辺 広昭, Project Period (FY)：1993 - 1994, Research Category：Grant-in-Aid for General Scientific Research (C), Research Field：Anesthesiology/Resuscitation studies

Actin assembly and inward flow in the plane of the immunological synapse (IS) drives the centralization of T cell receptor microclusters (TCR MCs) and the integrin leukocyte functional antigen 1 (LFA-1). Using structured-illumination microscopy (SIM), we show that actin arcs populating the medial, lamella-like region of the IS arise from linear actin filaments generated by one or more formins present at the IS distal edge. After traversing the outer, Arp2/3-generated, lamellipodia-like region of the IS, these linear filaments are organized by myosin II into antiparallel concentric arcs. Three-dimensional SIM shows that active LFA-1 often aligns with arcs, whereas TCR MCs commonly reside between arcs, and total internal reflection fluorescence SIM shows TCR MCs being swept inward by arcs. Consistently, disrupting actin arc formation via formin inhibition results in less centralized TCR MCs, missegregated integrin clusters, decreased T-B cell adhesion, and diminished TCR signaling. Together, our ...

PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

A panel of 21 alpha-subunit (CD11a) and 10 beta-subunit (CD18) anti-LFA-1 mAbs was screened for ability to activate LFA-1. A single anti-CD11a mAb, MEM-83, was identified which was able to directly induce the binding of T cells to purified ICAM-1 immobilized on plastic. This ICAM-1 binding could be achieved by monovalent Fab fragments of mAb MEM-83 at concentrations equivalent to whole antibody, was associated with appearance of the activation reporter epitope detected by mAb 24, and was completely inhibited by anti-ICAM-1 and LFA-1 blocking mAbs. The epitope recognized by mAb MEM-83 was distinct from that recognized by mAb NKI-L16, an anti-CD11a mAb previously reported to induce LFA-1 activation, in that it was constitutively present on freshly isolated peripheral blood mononuclear cells and was not divalent cation dependent for expression. The ICAM-1 binding activity induced by mAb MEM-83 was, however, dependent on the presence of Mg2+ divalent cations. Using an in vitro-translated CD11a ...

In this study, we have investigated whether SHIP plays a role in PMA- or cytokine-mediated LFA-1 activation by overexpressing both WT and phosphatase dead forms of SHIP in DA-ER cells. Our results show that 1) overexpression of WT-SHIP in unstimulated DA-ER cells increases LFA-1-mediated cell adhesion to ICAM-1, and this adhesion is further augmented by the addition of PMA, IL-3, or Epo; 2) SHIP requires a functional 5′-phosphatase domain for these effects, and overexpression of a phosphatase dead form actually leads to a slight inhibition of LFA-1-mediated adhesion to ICAM-1; 3) SHIP overexpression most likely enhances adhesion via its effect on inside-out signaling because its overexpression has no effect on the external activation of LFA-1 by Mn2+; 4) LFA-1 activation on cells overexpressing WT-SHIP does not involve activation of Erk-1 and Erk-2; and 5) LFA-1 activation in response to PMA in SHIP-overexpressing cells is via its effects on a PKC-stimulated pathway, while LFA-1 activation in ...

Jy kan nou jou gunsteling skoonheids-, gesondheids-, mode- en leefstylprodukte aanlyn koop Voelgoedwinkel. Sonder om n voet by die deur uit te sit én teen afslagpryse!

Jy kan nou jou gunsteling skoonheids-, gesondheids-, mode- en leefstylprodukte aanlyn koop Voelgoedwinkel. Sonder om n voet by die deur uit te sit én teen afslagpryse!