Ozone exposure enhances expression of cell-surface molecules associated with antigen-presenting activity on bronchoalveolar lavage cells in rats.
(49/437)
In this study, we investigated the effects of ozone (O3) exposure on expression of cell-surface molecules associated with antigen presentation and on accessory activity of bronchoalveolar lavage cells (BAL cells). Rats were exposed to 1 ppm O3 for 3 days. Expression of cell-surface molecules was measured by flow cytometry. Accessory activity of BAL cells was assessed by the allogeneic mixed lymphocyte reaction (MLR) and specific antigen-presenting activity. O3 exposure increased the expression of Ia, B7.1, B7.2, and CD11b/c on BAL cells. Morphological and immunological studies showed the Ia-positive cells to have monocyte-like features. Peripheral blood monocytes expressed Ia, B7.1, B7.2, and CD11b/c. The Ia expression on the monocytes was further increased by treatment of them with BAL fluid from O3-exposed rats (O3-BALF). Resident alveolar macrophages, however, did not express Ia antigen, and the Ia expression was not increased by O3-BALF. Neutrophils, which also infiltrated in response to O3 exposure, did not express Ia, B7.1, and B7.2. Therefore, infiltrating monocytes may have caused the increased expression of Ia and B7 molecules on BAL cells exposed to O3. The accessory activity of BAL cells in terms of MLR and specific antigen-presenting activity was also enhanced by O3 exposure. The present study suggests that monocytes infiltrating in response to O3 exposure caused enhancements of the expression of Ia and costimulatory molecules on and the accessory activity of BAL cells. (+info)
Mannose-binding lectin regulates the inflammatory response of human professional phagocytes to Neisseria meningitidis serogroup B.
(50/437)
The influence of the innate immune protein mannose-binding lectin (MBL) on the response of human phagocytes to Neisseria meningitidis was investigated. MBL increased the association of killed meningococci with neutrophils, monocytes, and macrophages by increasing the proportion of cells that recognized bacteria. MBL down-regulated the normal change in expression of the leukocyte adhesion molecules CD11b and CD62L. In an ex vivo model, the addition of MBL to the blood of MBL-deficient donors influenced the production of monocyte-derived inflammatory cytokines. The addition of high concentrations of MBL (>6 microg/mL) profoundly decreased the production of interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha by monocytes in response to meningococci, whereas lower concentrations enhanced the production of IL-6 and IL-1beta. These results suggest that MBL not only is involved in complement activation but also is a potent regulator of inflammatory pathways and, as such, may affect the severity of meningococcal disease. (+info)
Hydrodynamic shear regulates the kinetics and receptor specificity of polymorphonuclear leukocyte-colon carcinoma cell adhesive interactions.
(51/437)
The ability of tumor cells to metastasize hematogenously is regulated by their interactions with polymorphonuclear leukocytes (PMNs). However, the mechanisms mediating PMN binding to tumor cells under physiological shear forces remain largely unknown. This study was designed to characterize the molecular interactions between PMNs and tumor cells as a function of the dynamic shear environment, using two human colon adenocarcinoma cell lines (LS174T and HCT-8) as models. PMN and colon carcinoma cell suspensions, labeled with distinct fluorophores, were sheared in a cone-and-plate rheometer in the presence of the PMN activator fMLP. The size distribution and cellular composition of formed aggregates were determined by flow cytometry. PMN binding to LS174T cells was maximal at 100 s(-1) and decreased with increasing shear. At low shear (100 s(-1)) PMN CD11b alone mediates PMN-LS174T heteroaggregation. However, L-selectin, CD11a, and CD11b are all required for PMN binding to sialyl Lewis(x)-bearing LS174T cells at high shear (800 s(-1)). In contrast, sialyl Lewis(x)-low HCT-8 cells fail to aggregate with PMNs at high shear conditions, despite extensive adhesive interactions at low shear. Taken together, our data suggest that PMN L-selectin initiates LS174T cell tethering at high shear by binding to sialylated moieties on the carcinoma cell surface, whereas the subsequent involvement of CD11a and CD11b converts these transient tethers into stable adhesion. This study demonstrates that the shear environment of the vasculature modulates the dynamics and molecular constituents mediating PMN-tumor cell adhesion. (+info)
Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor-treated mice.
(52/437)
Interferon alpha/beta plays an important role in the first-line defense against viral infections and can modulate cytokine responses by T-helper cells. Type 1 interferons (IFNs) are clinically important in infectious diseases and in the treatment of leukemia and lymphomas. Many different cell types have the capacity to produce IFN-alpha after encounter with virus and bacteria. The major, natural type 1 IFN-producing cell in humans was recently described as the plasmacytoid T cell, or pDC2, and it can differentiate into dendritic cells (DCs) on culture. This study describes the murine natural IFN-alpha-producing cell, or pDC2, that shares morphologic features with its human counterpart but has some distinct phenotypical characteristics. Murine plasmacytoid DCs can be differentially isolated based on their expression of CD11c, B220 (CD45R), and Thy1.2 (CD90). They lack expression of myeloid (eg, CD11b) antigens and CD8 alpha, a marker used to isolate lymphoid DCs. Like human pDC2, murine plasmacytoid DCs exhibit their maximal type 1 IFN-producing capacity at a precursor stage; pDCs isolated from bone marrow responded to viral stimulation with higher IFN-alpha production than cells of the same phenotype isolated from spleen. Mobilization of mice with Flt3 ligand (Flt3L) or Flt3L and granulocyte-macrophage colony-stimulating factor, hematopoietic factors that specifically enhance DC growth, resulted in strikingly increased numbers of pDC in bone marrow and spleen. The isolation of this novel murine DC subset may serve as a useful tool in the study of viral immunobiology and for the design of treatments for murine malignancies. (+info)
Marked increase in number of dendritic cells in autoimmune-prone (NZW x BXSB)F1 mice with age.
(53/437)
Here, we report that the number of CD11c(+)CD3(-) B220(-) cells increases in autoimmune-prone male (NZW x BXSB)F1 (W/BF1) mice with age. The CD11c(+)CD3(-)B220(-) cells from W/BF1 mice show a typical stellate shape and induce the proliferation of T cells. In the CD11c(+)CD3(-)B220(-) cells from W/BF1 mice, CD11b (Mac-1alpha), NK 1.1, and CD95 (Fas) are upregulated in comparison with normal mice, while the expression of CD8alpha, CD117 (c-kit), CD135 (Flk-2/Flt-3), and Sca-1 decreases. There is a significant increase in Flt-3L (FL) mRNA in the bone marrow of W/BF1 mice with age. Moreover, activated hemopoietic cells express high levels of FL. The injection of CD11c(+)CD3(-)B220(-) cells from old W/BF1 mice to young W/BF1 mice transiently induces autoimmune disease (thrombocytopenia). These results suggest that hyperproduction of FL from activated hemopoietic cells induces a dramatic increase in the number of dendritic cells in aged W/BF1 mice, followed by the acceleration of autoimmunity. (+info)
Aldosterone and D-glucose stimulate the proliferation of human cardiac myofibroblasts in vitro.
(54/437)
The renin-angiotensin-aldosterone-system appears to be involved in the development of cardiac fibrosis in rodents, characterized by nonepithelial cell proliferation and changes in the extracellular matrix. The aim of our study was to investigate the effect of high aldosterone concentrations on the proliferation of human cardiac interstitial cells in vitro. In addition, the effect of D-glucose as another risk factor for fibrosis, eg, in the diabetic heart, was investigated. Human cardiac myofibroblast cultures were established, and growth rates were measured by WST-1 assay in fetal calf serum-free Dulbecco's modified Eagle's medium (DMEM). Cells in culture showed a significant increase in number between 24 to 72 hours of cultivation under basal conditions (DMEM, 10% fetal calf serum). Aldosterone at high concentrations (10(-8) and 10(-7) mol/L) significantly (P<0.01) increased the proliferation of cultured cardiac myofibroblasts. Comparable effects were observed after incubation of the cells with high D-glucose concentrations (15 and 25 mmol/L, P<0.01). No additive growth stimulation was evident when the cells were incubated in medium containing both aldosterone and D -glucose. These results suggest a role for aldosterone and glucose in mediating the cardiac fibrosis through stimulation of myofibroblast growth in patients with dysregulated renin-angiotensin-aldosterone-system (especially hyperaldosteronism) and impaired glucose homeostasis. (+info)
Fusion-defective gibbon ape leukemia virus vectors can be rescued by homologous but not heterologous soluble envelope proteins.
(55/437)
Murine leukemia virus (MLV)-derived envelope proteins containing alterations in or adjacent to the highly conserved PHQ motif present at the N terminus of the envelope surface subunit (SU) are incorporated into vector particles but are not infectious due to a postbinding block to viral entry. These mutants can be rendered infectious by the addition of soluble receptor-binding domain (RBD) proteins in the culture medium. The RBD proteins that rescue the infectivity of these defective MLV vectors can be derived from the same MLV or from other MLVs that use distinct receptors to mediate entry. We have now constructed functional immunologically reactive gibbon ape leukemia virus (GALV) envelope proteins, tagged with a feline leukemia virus (FeLV)-derived epitope tag, which are efficiently incorporated into infectious particles. Tagged GALV envelope proteins bind specifically to cells expressing the phosphate transporter protein Pit1, demonstrating for the first time that Pit1 is the binding receptor for GALV and not a coreceptor or another type of GALV entry factor. We have also determined that GALV particles bearing SU proteins with an insertion C-terminal to the PHQ motif (GALV I(10)) bind Pit1 but fail to infect cells. Incubation with soluble GALV RBD renders GALV I(10) particles infectious, whereas incubation with soluble RBDs from MLV or FeLV-B does not. This finding is consistent with the results obtained by Lauring et al. using FeLV-T, a virus that employs Pit1 as a receptor but requires soluble FeLV RBD for entry. MLV and GALV RBDs are not able to render FeLV-T infectious (A. S. Lauring, M. M. Anderson, and J. Overbaugh, J. Virol. 75:8888-8898, 2001). Together, these results suggest that fusion-defective FeLV-T and GALV are restricted to homologous RBD rescue of infectivity. (+info)
Preterminal host dendritic cells in irradiated mice prime CD8+ T cell-mediated acute graft-versus-host disease.
(56/437)
To understand the relationship between host antigen-presenting cells (APCs) and donor T cells in initiating graft-versus-host disease (GVHD), we followed the fate of host dendritic cells (DCs) in irradiated C57BL/6 (B6) recipient mice and the interaction of these cells with minor histocompatibility antigen- (miHA-) mismatched CD8+ T cells from C3H.SW donors. Host CD11c+ DCs were rapidly activated and aggregated in the T cell areas of the spleen within 6 hours of lethal irradiation. By 5 days after irradiation, <1% of host DCs were detectable, but the activated donor CD8+ T cells had already undergone as many as seven divisions. Thus, proliferation of donor CD8+ T cells preceded the disappearance of host DCs. When C3H.SW donor CD8+ T cells were primed in vivo in irradiated B6 mice or ex vivo by host CD11c+ DCs for 24-36 hours, they were able to proliferate and differentiate into IFN-gamma-producing cells in beta(2)-microglobulin-deficient (beta(2)m(-/-)) B6 recipients and to mediate acute GVHD in beta(2)m(-/-) --> B6 chimeric mice. These results indicate that, although host DCs disappear rapidly after allogeneic bone marrow transplantation, they prime donor T cells before their disappearance and play a critical role in triggering donor CD8+ T cell-mediated GVHD. (+info)