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At least 397 records · Page 22Linked to original sources
PubMed1981

Pulmonary response and transmigration of inorganic fibers by inhalation exposure.

Rats, hamsters, and guinea pigs were exposed by inhalation to different concentrations of potassium octatitanate fibers. Following 3 months of exposure, the animals were sacrificed between the 15th and 24th month. The exposed animals showed dose-related dust deposition and pulmonary fibrosis mainly in the respiratory bronchiolar region. Most short fibers (less than 5 micrograms) were phagocytized by alveolar macrophages, but long fibers (greater than 10 micrograms) were phagocytized by foreign body giant cells. Dust-laden macrophages (dust cells) entered into the lumen of bronchial lymphatic or pulmonary blood vessels. Numerous dust cells were transported from the lung to the tracheobronchial and mediastinal lymph nodes where some dust cells penetrated into the blood or lymphatic circulation. Massive direct cell migration of the mediastinal adipose tissue from the lymph nodes occurred occasionally. Dust-laden giant cells were found only occasionally in the liver, and there was widespread migration of the fibers into other vital organs and tissues without any significant responses.

Animals↗
PubMed1995

T cell gelatinases mediate basement membrane transmigration in vitro.

T cell homing into extravascular sites requires penetration across the subendothelial basal lamina, a specialized nonfibrillar connective tissue structure that anchors endothelial cells to parenchymal surfaces. Herein, we show that normal human T cells express gelatinases A and B, two matrix metalloproteinases active against the major basal lamina constituents, collagen types IV and V. Expression is confirmed at both the mRNA and protein levels. Gelatinase B is expressed constitutively, whereas gelatinases A and B expression is induced by T cell activation. In vitro migration of resting T cells across a basal lamina equivalent is mediated by gelatinase B, because it is specifically blocked by GM6001, a hydroxamic acid inhibitor of matrix metalloproteinases. Inhibition of T cell homing by interference with gelatinase function may represent a useful approach to the treatment of T cell-mediated autoimmune diseases.

Base Sequence↗
PubMed1996

Salicylates inhibit I kappa B-alpha phosphorylation, endothelial-leukocyte adhesion molecule expression, and neutrophil transmigration.

The expression of leukocyte adhesion molecules on endothelial cells is induced by TNF-alpha and other inflammatory cytokines. This induction of endothelial-leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 requires the transcription factor nuclear factor-kappa B (NF-kappa B). Recent work has suggested that some nonsteroidal anti-inflammatory agents, including sodium salicylate and aspirin, can inhibit NF-kappa B-dependent gene activation. We studied the effects of salicylates on expression of adhesion molecules in HUVECs. We found that sodium salicylate inhibited activation of NF-kappa B (p50/p65 and p65/p65) by preventing phosphorylation and subsequent degradation of the inhibitor 1 kappa B-alpha. Salicylate treatment had no effect on TNF-alpha-induced phosphorylation of the transcription factor ATF-2. Salicylate blocked the TNF-alpha-induced increase in mRNA levels of adhesion molecules and gave a dose-dependent inhibition of TNF-alpha-induced surface expression of vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 with higher doses required to inhibit endothelial-leukocyte adhesion molecule-1 expression. Indomethacin, a nonsalicylate cyclooxygenase inhibitor, had no effect on surface expression of adhesion molecules, suggesting that the effects were not due to inhibition of cyclooxygenase. Treatment of endothelial cell monolayers with sodium salicylate inhibited transendothelial migration of neutrophils but had no significant effect on neutrophil adhesion under flow conditions. The clinical importance of high-dose salicylates in inflammation may be due, in part, to the ability to prevent expression of inducible adhesion molecules and recruitment of leukocytes.

Base Sequence↗
PubMed2002

Methylprednisolone acts on peripheral blood mononuclear cells and endothelium in inhibiting migration phenomena in patients with multiple sclerosis.

BACKGROUND: Intravenous methylprednisolone hemisuccinate is administered to patients with multiple sclerosis (MS) during exacerbations to improve the rate of recovery. Corticosteroids could be beneficial in MS exacerbations also by decreasing transmigration of peripheral blood mononuclear cells (PBMNCs) through the blood-brain barrier. OBJECTIVES: To evaluate how in vivo intravenous methylprednisolone treatment in patients with MS could influence transmigration of PBMNCs in an in vitro model; to perform transmigration experiments through a methylprednisolone-treated endothelium with PBMNCs from untreated healthy control subjects to evaluate putative selective effects of corticosteroids on endothelium; concomitantly, to quantify the concentration of matrix metalloproteinases 2 and 9 in supernatants of PBMNCs and in serum samples from methylprednisolone-treated patients with MS; to evaluate monokine induced by interferon-gamma release in the supernatants of human umbilical vein endothelial cells treated with interferon-gamma alone or interferon-gamma and methylprednisolone; and to perform gene expression studies of matrix metalloproteinases 2 and 9 in human umbilical vein endothelial cells and PBMNCs from methylprednisolone-treated patients with MS. PATIENTS: Eight patients with MS in exacerbation were studied before and 3 and 24 hours after intravenous methylprednisolone treatment, 1 g. RESULTS: The absolute number of transmigrated PBMNCs from methylprednisolone-treated patients with MS significantly (P<.01) decreased at 3 hours and increased again at 24 hours, reaching values higher than those before treatment onset. Methylprednisolone was also able to significantly (P<.03) reduce the number of PBMNCs from healthy controls migrating through interferon-gamma-stimulated or unstimulated endothelium. In vitro methylprednisolone treatment decreased monokine induced by interferon-gamma production in human umbilical vein endothelial cells. CONCLUSIONS: Methylprednisolone may be able to decrease transmigration of PBMNCs through the blood-brain barrier, exerting its inhibitory effects on PBMNCs and endothelium. A "rebound" of transmigration at 24 hours suggests that a single infusion is not optimal for achieving a persistent reduction in transmigration.

Adult↗
PubMed2000

Shear stress affects migration behavior of polymorphonuclear cells arrested on endothelium.

Polymorphonuclear cell (PMN) transmigration across the TNF-alpha-stimulated endothelial cell (HUVEC) monolayer in the presence of shear flow was monitored with time-lapse videotapes. More than half of the PMN that arrested on HUVEC transmigrated through endothelial cell junctions within the following 15 min. The kinetics of transmigration was significantly faster than that of PMN placed under static conditions. Once PMN crept into the subendothelial space, they showed random migration beneath the HUVEC monolayer. PMN that did not transmigrate moved on the apical surface of HUVEC in the direction of flow downstream. Anti-beta1 integrin mAb (4B4) and RGD peptide inhibited the transmigration more effectively than anti-beta2 integrin mAb (TS1/18) and almost totally abrogated transmigration. When HUVEC were cultured on fibronectin or laminin, the transmigration was significantly inhibited by anti-alpha5 or alpha6 integrin mAbs, respectively. Our data clearly indicate that shear stress affects the migration behavior of PMN arrested on endothelium and suggest that binding to subendothelial extracellular matrix via beta1 integrins is another essential step in leukocyte extravasation.

Antigens, CD↗
PubMed1994

The induction of 72-kD gelatinase in T cells upon adhesion to endothelial cells is VCAM-1 dependent.

T cell extravasation from the bloodstream into the perivascular tissue during inflammation involves transmigration through the endothelial cell layer and basement membrane into the interstitial matrix. The specific mechanisms by which T cells transmigrate, however, are poorly understood. Matrix degradation by enzymes such as 72-kD gelatinase has been implicated as an important component in tissue invasion by various types of cells. In this study, we have demonstrated that 72-kD gelatinase is induced in T cells upon adhesion to endothelial cells. We also provide evidence that the induction of 72-kD gelatinase is mediated by binding to vascular cell adhesion molecule-1 (VCAM-1). The T cells used in this study were cloned murine Th1 cells antigenic to myelin basic protein. These cells express very late antigen-4 on their cell surface and have been shown to infiltrate the brain parenchyma and cause experimental autoimmune encephalomyelitis when infused into normal mice (Baron, J. L., J. A. Madri, N. H. Ruddle, G. Hashim, and C. A. Janeway. 1993. J. Exp. Med. 177:57-68). In the experiments presented here, T cells were cocultured with VCAM-1-positive and -negative endothelial cells grown in a monolayer in order to study the expression of 72-kD gelatinase upon T cell adhesion. Additional experiments were conducted in which T cells were cocultured with VCAM-1 positive cells grown on microporous membranes suspended in transwells to study 72-kD gelatinase following T cell transmigration. T cells were also incubated with recombinant VCAM-1 in order to study the role of VCAM-1 in inducing 72-kD gelatinase. The results demonstrated that T cells adhered to both VCAM-1-positive and -negative endothelial cells. T cells that adhered to the VCAM-1-positive endothelial cells exhibited an induction in 72-kD gelatinase protein, activity, and mRNA whereas 72-kD gelatinase was not induced in the T cells that adhered to the VCAM-1-negative endothelial cells. Incubating T cells with recombinant VCAM-1 coated onto tissue culture plastic showed that T cells adhered to the molecule and that adhesion to recombinant VCAM-1 was sufficient to induce 72-kD gelatinase. Further, T cells that had transmigrated through a VCAM-1-positive endothelial cell monolayer exhibited 72-kD gelatinase activity but not mRNA expression. In addition, 72-kD gelatinase was detected on the cell surface of the transmigrated T cells by FACS analysis. In other experiments, TIMP-2 was added to the transmigration studies and was shown to reduce T cell transmigration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

VLA-4-dependent and -independent pathways in cell contact-induced proinflammatory cytokine production by synovial nurse-like cells from rheumatoid arthritis patients.

Nurse-like stromal cell lines from the synovial tissue of patients with rheumatoid arthritis (RA-SNC) produce, on coculture with lymphocytes, large amounts of proinflammatory cytokines. In the present paper, we analyze the molecular events necessary for the induction of cytokine release from RA-SNC cells, and particularly the roles played by cell adhesion and the transmigration (also known as pseudoemperipolesis) of lymphocytes. For this purpose, the effects of various mAbs on the binding and transmigration of a human B-cell line, MC/car, were examined using a cloned RA-SNC line, RA-SNC77. To analyze the role of lymphocyte binding and transmigration on upregulated cytokine production by the RA-SNC77 cells, we used C3 exoenzyme-treated MC/car cells, which could bind to RA-SNC77 cells but could not transmigrate. Treatment with anti-CD29 or anti-CD49d mAb significantly reduced binding and transmigration of the MC/car cells. In contrast, the neutralizing anti-CD106/vascular cell adhesion molecule 1 mAb did not show any inhibitory effect. Likewise, none of the neutralizing mAbs against CD11a, CD18, CD44, CD49e, or CD54 showed significant effects. Binding of C3-treated or untreated MC/car cells to RA-SNC77 cells induced comparable levels of IL-6 and IL-8 production. In addition, the enhanced cytokine production by RA-SNC77 cells required direct lymphocyte contact via a very late antigen-4 (VLA-4)-independent adhesion pathway. These results indicate that, although both the VLA-4-dependent/vascular cell adhesion molecule 1-independent and the VLA4-independent adhesion pathways are involved in MC/car binding and subsequent transmigration, only the VLA4-independent adhesion pathway is necessary and sufficient for the enhanced proinflammatory cytokine production by RA-SNC77 cells. The transmigration process, which is dependent on Rho-GTPase, is not a prerequisite for this phenomenon.

Antibodies, Monoclonal↗
PubMed1999

Xenogeneic serum promotes leukocyte-endothelium interaction under flow through two temporally distinct pathways: role of complement and nuclear factor-kappaB.

Endothelial cell activation and mononuclear cell infiltration are consistent features of discordant xenograft rejection. This study evaluated whether xenogeneic serum--as a source of xenoreactive natural antibodies and complement--induced endothelial activation with consequent leukocyte adhesion and transmigration under flow conditions. Porcine aortic endothelial cells (PAEC) were incubated for 30 min, 1 h 30 min, or 5 h with 10% human serum or 10% porcine serum and then perfused with human leukocytes in a parallel plate flow chamber under flow (1.5 dynes/cm2). Adherent and transmigrated cells were counted by digital image analysis. Results showed that human serum significantly (P < 0.01) increased over time the number of adherent leukocytes compared with porcine serum. Stimulation of PAEC with human serum also promoted a progressive increase in leukocyte transmigration that reached statistical significance (P < 0.01) at 1 h 30 min and at 5 h compared with porcine serum. Studying the role of complement in leukocyte-endothelium interaction in xenogeneic conditions, a marked complement C3 deposition on PAEC exposed to human serum was shown by immunofluorescence, whereas cells incubated with porcine serum were negative. Next, it was documented that human serum decomplemented by heating and C3-deficient human serum failed to promote both leukocyte adhesion and transmigration, results that were comparable to porcine serum. To elucidate the intracellular mediators involved in endothelial cell activation by xenogeneic serum, this study focused on transcriptional factor nuclear factor-kappaB (NF-kappaB), a central regulator for the induction of different genes, including adhesive molecules and chemoattractants. Positive nuclear staining of NF-kappaB (p65 subunit) found by confocal fluorescence microscopy of PAEC exposed to human serum was taken to reflect NF-kappaB activation. NF-kappaB was instead strictly localized in the cell cytoplasm in PAEC incubated with the homologous serum. Heat-inactivated human serum failed to activate NF-kappaB. Electrophoretic mobility shift assay of nuclear extracts from PAEC exposed to human serum revealed an intense NF-kappaB activation that was inhibited by the NF-kappaB inhibitor pyrrolidinedithiocarbamate. The NF-kappaB inhibitors pyrrolidinedithiocarbamate and tosyl-phe-chloromethylketone did not affect the number of adherent and transmigrated leukocytes in PAEC exposed to human serum for 30 min and 1 h 30 min. Both inhibitors instead significantly reduced leukocyte adhesion and transmigration induced by human serum at 5 h. Confocal fluorescence microscopy studies showed that human serum induced an increase in the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. Functional blocking of these adhesive molecules with the corresponding antibodies significantly inhibited xenogeneic serum-induced leukocyte adhesion. These data suggest that leukocyte adhesion and transmigration are directly dependent on complement deposited on PAEC in the early phase of cell activation (30 min and 1 h 30 min) induced by xenogeneic serum, whereas leukocyte adhesive events observed after 5 h of incubation of endothelial cells with xenogeneic serum are possibly regulated by transcription of NF-kappaB-dependent genes. The finding that xenogeneic serum promotes leukocyte-endothelial interaction depending on NF-kappaB activation might be relevant for designing future therapeutic strategies intended to prolong xenograft survival.

Animals↗
PubMed1993

Studies of lymphocyte transendothelial migration: analysis of migrated cell phenotypes with regard to CD31 (PECAM-1), CD45RA and CD45RO.

CD31 is a 130,000 MW cell-surface glycoprotein expressed on endothelial cells, polymorphonuclear leucocytes, monocytes and about 50% of peripheral blood lymphocytes, and it has been proposed that it plays a role in transendothelial migration. If it is involved in endothelial transmigration of lymphocytes then the proportion of CD31+ cells should be increased in the lymphocyte population which has crossed an endothelial monolayer. This was tested using two endothelial types, namely human umbilical vein endothelial cells (HUVEC) and rat high endothelial venule (RHEV) cells. As a control, lymphocyte CD45RA and CD45RO expression was also determined since there is a correlation between lymphocytes bearing these isoforms and different migratory patterns. Double labelling techniques showed a close correlation between CD31 and CD45RA expression. With HUVEC monolayers, the transmigrated lymphocyte population was depleted of CD31+ cells. This depletion was even more marked if the HUVEC monolayers had been stimulated with interleukin-1 beta (IL-1 beta). The migrated lymphocytes were enriched for CD31-CD45RO+ cells but depleted of CD31+CD45RA+ cells. In addition, lymphocyte populations depleted of CD31+ cells by immunopanning were also able to migrate across HUVEC monolayers. Taken together these data suggest that lymphocyte CD31 expression is not necessary for transmigration across HUVEC monolayers and, if anything, is negatively correlated with transmigration. With the second endothelial cell type, RHEV cells, there was no consistent change in the proportion of CD31+ lymphocyte in the transmigrated population, suggesting neither a positive nor a negative correlation between CD31+ expression and lymphocyte transmigration across RHEV cells. However, with both endothelial cell types, the migrated lymphocyte populations were enriched for the marker CD45RO. In conclusion, lymphocyte surface expression of CD31 is not necessary for transmigration across the endothelial cell types used in this study, but with both cell types an enrichment of CD45RO+ lymphocytes is seen in the migrated population.

Antigens, Differentiation, Myelomonocytic↗
PubMed1997

Transendothelial migration of CD34+ and mature hematopoietic cells: an in vitro study using a human bone marrow endothelial cell line.

To study the role of bone marrow endothelial cells (BMEC) in the regulation of hematopoietic cell trafficking, we have designed an in vitro model of transendothelial migration of hematopoietic progenitor cells and their progeny. For these studies, we have taken advantage of a human BMEC-derived cell line (BMEC-1), which proliferates independent of growth factors, is contact inhibited, and expresses adhesion molecules similar to BMEC in vivo. BMEC-1 monolayers were grown to confluency on 3 microns microporous membrane inserts and placed in 6-well tissue culture plates. Granulocytecolony stimulating factor (G-CSF)-mobilized peripheral blood CD34+ cells were added to the BMEC-1 monolayer in the upper chamber of the 6-well plate. After 24 hours of coincubation, the majority of CD34+ cells remained nonadherent in the upper chamber, while 1.6 +/- 0.3% of the progenitor cells had transmigrated. Transmigrated CD34 cells expressed a higher level of CD38 compared with nonmigrating CD34+ cells and may therefore represent predominantly committed progenitor cells. Accordingly, the total plating efficiency of the transmigrated CD34+ cells for lineage-committed progenitors was higher (14.0 +/- 0.1 v 7.8% +/- 1.5%). In particular, the plating efficiency of transmigrated cells for erythroid progenitors was 27-fold greater compared with nonmigrating cells (8.0% +/- 0.8% v 0.3% +/- 0.1%) and 5.5-fold compared with unprocessed CD34+ cells (2.2% +/- 0.4%). While no difference in the expression of the beta 1-integrin very late activation antigen (VLA)-4 and beta 2-integrin lymphocyte function-associated antigen (LFA)-1 was found, L-selectin expression on transmigrated CD34+ cells was lost, suggesting that shedding had occurred during migration. The number of transmigrated cells was reduced by blocking antibodies to LFA-1, while L-selectin and VLA-4 antibodies had no inhibitory effect. Continuous coculture of the remaining CD34+ cells in the upper chamber of the transwell inserts resulted in proliferation and differentiation into myeloid and megakaryocytic cells. While the majority of cells in the upper chamber comprised proliferating myeloid precursors such as promyelocytes and myelocytes, only mature monocytes and granulocytes were detected in the lower chamber. In conclusion, BMEC-1 cells support transmigration of hematopoietic progenitors and mature hematopoietic cells. Therefore, this model may be used to study mechanisms involved in mobilization and homing of CD34+ cells during peripheral blood progenitor cell transplantation and trafficking of mature hematopoietic cells.

Antigens, CD34↗