Amnion-derived cells express intercellular adhesion molecule-1: regulation by cytokines.
(41/5011)
We have examined the expression of the intercellular adhesion molecule-1 (ICAM-1) mRNA in primary and established amnion-derived cell cultures and regulation of this expression by tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta. TNF-alpha (50 ng/ml) and IL-1beta (1.0 ng/ml) induced 18- and 11-fold increases respectively in expression of the ICAM-1 mRNA in WISH cells (an amnion epithelium-derived cell line). The increase was detectable within one hour of treatment and peaked by two hours. The protein synthesis inhibitor, cycloheximide (10 microg/ml) did not inhibit this induction. Increased levels of ICAM-1 protein were detected in the cells within 4 h after initiation of treatment with either cytokine. By 16 h of treatment with IL-1beta or TNF-alpha ICAM-1 reached 40 and 73 pg/microg cellular protein, representing 6- and 11-fold stimulations respectively. In primary amnion cells, basal expression of ICAM-1 mRNA was undetectable. However, TNF-alpha (50 ng/ml) induced ICAM-1 mRNA within two hours, peak expression being reached between four and eight hours after initiation of treatment. The present report demonstrates for the first time that amnion derived cells can express ICAM-1 and, further, that this expression is regulated by pro-inflammatory cytokines. This has implications for the amnion as a possible source for soluble ICAM-1, for this gene product as a marker for preterm labour, and for participation of the amnion, additional to its reported secretory role, in inflammatory processes of the fetal membranes. (+info)
Human follicular dendritic cells remain uninfected and capture human immunodeficiency virus type 1 through CD54-CD11a interaction.
(42/5011)
It has been reported that human immunodeficiency virus type 1 (HIV-1) bound to follicular dendritic cells (FDCs) remains highly infectious to CD4(+) T cells even when it forms immune complexes with neutralizing antibody (HIV-1/IC). To elucidate the role of FDCs in HIV-1 transmission to CD4(+) T cells in lymph nodes, we have isolated and purified FDCs from human tonsils and examined whether the HIV-1/IC trapped on their surface is infectious to CD4(+) T cells. To our surprise, not the HIV-1/IC but the antibody-free HIV-1 on FDCs could be transmitted to CD4(+) T cells. Furthermore, in contrast to previous studies showing that FDCs are productively infected with HIV-1, the present study clearly demonstrated that FDCs were not the target cells for HIV-1 infection. FDCs could capture the viral particles on their surface; however, the binding of HIV-1 to FDCs was strongly inhibited by the presence of anti-CD54 (ICAM-1) monoclonal antibody (MAb) and anti-CD11a (LFA-1) MAb, suggesting that the adhesion molecules play an important role in the interaction between HIV-1 and FDCs. (+info)
A critical role for a peritumoral stromal reaction in the induction of T-cell migration responsible for interleukin-12-induced tumor regression.
(43/5011)
Interleukin (IL) 12 has been shown to elicit tumor regression when this cytokine induces the migration of T cells to tumor sites. The present study investigates the role of a peritumoral stromal reaction in IL-12-induced T-cell migration. In the CSA1M and OV-HM tumor models, IL-12 treatment induced tumor regression that is associated with T-cell migration. Neither T-cell migration nor tumor regression was observed in the Meth A and MCH-1-A1 models. Stromal tissue containing neovascular blood vessels developed at the peritumoral area of the former two IL-12-responsive tumors but not at the peritumoral area of the latter two IL-12-unresponsive tumors. The significance of stroma development was investigated using a pair of tumor models (CSA1M and a subline derived from CSA1M designated the CSA1M variant), both of which exhibit the same tumor immunogenicity. In contrast to the parental CSA1M cell line, the variant cell line was not responsive to IL-12, and neither stroma development nor T-cell migration was observed, even after IL-12 treatment. Histological analyses revealed that the parental cell line had peritumoral stroma with intrastromal vessels but only a few vessels in tumor parenchyma, whereas the variant cell line showed no stroma but had abundant vasculature in the tumor parenchyma. Most importantly, only stromal vessels in the parental tumors expressed detectable and enhanced levels of vascular cell adhesion molecule 1 (VCAM-1)/ intercellular adhesion molecule 1 (ICAM-1) before and after IL-12 treatment, respectively. In contrast, parenchymal vasculature in the variant cell line failed to express VCAM-1/ICAM-1 even after IL-12 treatment. When transferred into recipient tumor-bearing mice, IL-12-stimulated T cells from the parental CSA1M-bearing or the variant CSA1M-bearing mice migrated into the parental but not into the variant tumor mass. Together with our previous finding that T-cell migration depends on the VCAM-1/ICAM-1 adhesive interactions, the present results indicate a critical role for peritumoral stroma/stromal vasculature in the acceptance of tumor-infiltrating T cells that is a prerequisite for IL-12-induced tumor regression. (+info)
Assessment of the mechanism of juxtacrine activation and adhesion of leukocytes in liver microcirculation.
(44/5011)
Leukotriene C4 (LTC4), histamine, and other mediators can induce expression of P-selectin and platelet-activating factor (PAF) on venular endothelium to recruit leukocytes in vivo and in vitro via a juxtacrine mechanism of adhesion. The objective of this study was to assess the effect of histamine and LTC4 on the leukocyte recruitment in the liver and to study the components and molecular mechanisms involved in this process. We visualized the hepatic microvasculature using intravital microscopy and we determined that LTC4 (20 nM) but not histamine (0.1, 0.3, or 1 mM) induced leukocyte recruitment in the liver microcirculation. Histamine could induce leukocyte recruitment but only in the presence of an antihistaminase. The LTC4-induced leukocyte recruitment occurred primarily in sinusoids (not venules) and was not inhibitable by three different anti-P-selectin antibodies (5H1, RMP-1, and RB40). Leukocyte recruitment in P-selectin-deficient mice, intercellular adhesion molecule 1 (ICAM-1)-deficient mice, and mice treated with a PAF antagonist was of the same magnitude as in wild-type animals in response to LTC4. Although PAF alone could induce adhesion in both sinusoids and postsinusoidal venules, this chemotactic agent was not involved in LTC4-induced adhesion in the liver. Finally, an overlapping role for P-selectin and ICAM-1 was ruled out as LTC4 induced leukocyte recruitment in P-selectin and ICAM-1 double-deficient mice. These data demonstrate that LTC4 does not activate the known early mechanisms of leukocyte recruitment, including P-selectin, PAF, or ICAM-1 in the hepatic microvasculature. (+info)
Mechanisms underlying the anti-inflammatory actions of central corticotropin-releasing factor.
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Immune activation of hypothalamic corticotropin-releasing factor (CRF) provides a negative feedback mechanism to modulate peripheral inflammatory responses. We investigated whether central CRF attenuates endothelial expression of intercellular adhesion molecule 1 (ICAM-1) and leukocyte recruitment during endotoxemia in rats and determined its mechanisms of action. As measured by intravital microscopy, lipopolysaccharide (LPS) induced a dose-dependent increase in leukocyte rolling, adhesion, and emigration in mesenteric venules, which was associated with upregulation of endothelial ICAM-1 expression. Intracisternal injection of CRF abrogated both the increased expression of ICAM-1 and leukocyte recruitment. Intravenous injection of the specific CRF receptor antagonist astressin did not modify leukocyte-endothelial cell interactions induced by a high dose of LPS but enhanced leukocyte adhesion induced by a low dose. Blockade of endogenous glucocorticoids but not alpha-melanocyte-stimulating hormone (alpha-MSH) receptors reversed the inhibitory action of CRF on leukocyte-endothelial cell interactions during endotoxemia. In conclusion, cerebral CRF blunts endothelial upregulation of ICAM-1 and attenuates the recruitment of leukocytes during endotoxemia. The anti-inflammatory effects of CRF are mediated by adrenocortical activation and additional mechanisms independent of alpha-MSH. (+info)
Effect of selective proteasome inhibitors on TNF-induced activation of primary and transformed endothelial cells.
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The objective of this study was to assess the effects of two structurally distinct yet selective proteasome inhibitors (PS-341 and lactacystin) on leukocyte adhesion, endothelial cell adhesion molecule (ECAM) expression, and nuclear factor-kappaB (NF-kappaB) activation in tumor necrosis factor (TNF)-alpha-stimulated human umbilical vein endothelial cells (HUVEC) and the transformed, HUVEC-derived, ECV cell line. We found that TNF (10 ng/ml) significantly enhanced U-937 and polymorphonuclear neutrophil (PMN) adhesion to HUVEC but not to ECV; TNF also significantly enhanced surface expression of vascular cell adhesion molecule 1 and E-selectin (in HUVEC only), as well as intercellular adhesion molecule 1 (ICAM-1; in HUVEC and ECV). Pretreatment of HUVEC with lactacystin completely blocked TNF-stimulated PMN adhesion, partially blocked U-937 adhesion, and completely blocked TNF-stimulated ECAM expression. Lactacystin attenuated TNF-stimulated ICAM-1 expression in ECV. Pretreatment of HUVEC with PS-341 partially blocked TNF-stimulated leukocyte adhesion and ECAM expression. These effects of lactacystin and PS-341 were associated with inhibitory effects on TNF-stimulated NF-kappaB activation in both HUVEC and ECV. Our results demonstrate the importance of the 26S proteasome in TNF-induced activation of NF-kappaB, ECAM expression, and leukocyte-endothelial adhesive interactions in vitro. (+info)
Expression of the lymphotoxin beta receptor on follicular stromal cells in human lymphoid tissues.
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The lymphotoxin beta receptor (LTbetaR), and its ligand, LTalpha1beta2, have been proposed to play a key role in the development and organization of lymphoid tissues. The LTbetaR is expressed on a variety of human primary and transformed cells, but strikingly absent on T or B lymphocytes and primary monocytes or peripheral dendritic cells, although LTbetaR is detected on some myeloid leukemic lines. In the developing thymus LTbetaR is prominent along the trabeculae and into the medulla upto corticomedullary junction. In the spleen, LTbetaR is prominently expressed by cells in the red pulp and along the borders of red and white pulp which colocalizes with reticular stromal cells. The LTbetaR is expressed on a human follicular dendritic cell line, FDC-1, and signals expression of CD54 when ligated with the LTalpha1beta2 complex. These results support the concept that directional interactions between LTalpha1beta2 bearing lymphocytes and LTbetaR bearing stromal cells are involved in the organization of lymphoid tissue. (+info)
Interleukin-4 ameliorates crescentic glomerulonephritis in Wistar Kyoto rats.
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BACKGROUND: Activated macrophages play a central role in crescentic glomerulonephritis. Interleukin-4 (IL-4) down-regulates many macrophage proinflammatory activities. We therefore studied the effect of IL-4 on glomerular injury in a model of crescentic glomerulonephritis in the Wistar Kyoto rat. METHODS: Glomerulonephritis was induced by i.v. administration of rabbit antirat glomerular basement membrane antiserum (nephrotoxic serum, NTS). In experiment 1, IL-4 was given from two hours before NTS until day 6. In experiment 2, rats were treated from day 0 to 7 and were then monitored until killed on day 28. In experiment 3, IL-4 was given from day 4 to 7. RESULTS: Continuous IL-4 treatment (experiment 1) significantly (P = 0.001) reduced proteinuria (3 +/- 1 mg per 24 hr vs. 56 +/- 7), fibrinoid necrosis (0.06 +/- 0.04 quadrants/glomulus vs. 1.2 +/- 0.1), macrophage infiltration (6.7 +/- 2.6 cells/glom vs. 33 +/- 2.5), CD8+ cells (1.5 +/- 0.6 cells/glom vs. 6.2 +/- 1.1), inducible nitric oxide synthase positive cells (0.04 +/- 0.04 cells/glom vs. 3.7 +/- 0.6), proliferating cell nuclear antigen positive cells (3.2 +/- 1 cells/glom vs. 15 +/- 2.3), and glomerular intercellular adhesion molecule-1 expression. Follow-up after seven days of treatment (experiment 2) showed that at four weeks, creatinine clearance was higher in treated rats (1.1 +/- 0.1 ml/min vs. 0.4 +/- 01, P = 0.011), and both glomerular scarring (P = 0.006) and tubular atrophy (P = 0.006) were less. Delayed treatment (experiment 3) reduced proteinuria (41 +/- 5 mg per 24 hr vs. 97 +/- 9, P = 0.004) and fibrinoid necrosis (0.39 +/- 0.05 quadrants/glom vs. 1.6 +/- 0.1, P = 0.004). There was no difference in macrophage infiltration, but inducible nitric oxide synthase positive cells were reduced (0.6 +/- 0.1 cells/glom vs. 1.8 +/- 0.4, P = 0.01) as were ED3+ cells (0.18 +/- 0.06 cells/glom vs. 1.86 +/- 0.21, P = 0.004). CONCLUSION: In this model of crescentic glomerulonephritis, early IL-4 treatment abolished proteinuria and markedly reduced glomerular inflammation. If treatment was stopped after seven days, there was continuing benefit on glomerular and tubulointerstitial scarring and creatinine clearance at four weeks. If treatment was delayed until inflammation was established, there was still a reduction of injury, but without an alteration of macrophage numbers, suggesting that IL-4 may be acting, in part, to reduce macrophage activation. (+info)