Home About us Contact
|
Home About us Contact | ||
|
|
||
Transendothelial Migration (transendothelial + migration)
Kinds of Transendothelial Migration Selected AbstractsAgonists of proteinase-activated receptor-2 affect transendothelial migration and apoptosis of human neutrophilsEXPERIMENTAL DERMATOLOGY, Issue 10 2007Victoria M. Shpacovitch Abstract:, Skin is the first barrier preventing microorganism invasion in host. Wounds destroy this defense barrier and, without an appropriate care, may lead to sepsis. Neutrophil activation and immigration plays an important role at the inflammatory stage of wound healing. Neutrophils are known to express proteinase-activated receptors (PARs), which can be activated by serine proteases, also by enzymes involved in wound healing. We previously reported that PAR2 agonists up-regulate cell adhesion molecule expression and cytokine production by human neutrophils. Here, we demonstrate that PAR2 agonists (serine proteases as well as synthetic peptides) reduce transendothelial migration of neutrophils and prolong their life in vitro. Synthetic PAR2 agonist also enhanced protective interferon (IFN),-induced Fc,RI expression at neutrophil cell surface. Of note, IFN, is a cytokine, which was used in clinical trials to reactivate human neutrophil functions during sepsis. Moreover, we observed a significant increase of PAR2 expression on cell surface of neutrophils from septic patients as compared with healthy volunteers. Together, our results indicate that PAR2 may be involved in the pathophysiology of neutrophil-endothelial interactions during wound healing or later during sepsis in humans, potentially by affecting neutrophil apoptosis, transendothelial migration and Fc, receptor-mediated phagocytosis. [source] Structure, lymphatic vascularization and lymphocyte migration in mucosa-associated lymphoid tissueIMMUNOLOGICAL REVIEWS, Issue 1 2003Giacomo Azzali Summary:, In this review, we consider the morphological aspects and topographical arrangement of gut-associated lymphoid tissue (GALT) (solitary and aggregate lymph nodules or Peyer's patches) and of vermiform appendix in the human child and in some mammals. The spatial arrangement of the vessels belonging to apparatus lymphaticus periphericus absorbens (ALPA) and of blood vessels within each lymphoid follicle as well as the ultrastructural characteristics of the lymphatic endothelium with high absorption capacity are considered. Particular attention is also paid to the morphological and biomolecular mechanisms inducing lymphocyte transendothelial migration to the bloodstream by means of lymphatic vessels as well as their passage from blood into lymphoid tissue through the high endothelial venules (HEVs). The preferential transendothelial passage of lymphocytes and polymorphonuclear neutrophils within ALPA vessels of the interfollicular area does not occur following the opening of intercellular contacts, but rather it occurs by means of ,intraendothelial channels'. In HEVs, on the contrary, the hypothesis is plausible that lymphocyte transendothelial migration into lymphoid tissue occurs through a channel-shaped endothelial invagination entirely independent of interendothelial contacts. The lymph of ALPA vessels of the single Peyer's patch is conveyed into precollector lymphatic vessels and into prelymph nodal collectors, totally independent of the ALPA vessels of the gut segments devoid of lymphoid tissue. The quantitative distribution of T lymphocytes in the lymph of mucosal ALPA vessels suggests a prevalent function of fluid uptake, whereas a reservoir and supply function is implicated for the vessels of interfollicular area. The precollector lymphatic vessels and prelymph nodal collectors are considered to be vessels with low absorption capacity, whose main function is lymph conduction and flow. [source] The Fps/Fes kinase regulates leucocyte recruitment and extravasation during inflammationIMMUNOLOGY, Issue 4 2007Sean A. Parsons Summary Fps/Fes and Fer comprise a distinct subfamily of cytoplasmic protein-tyrosine kinases, and have both been implicated in the regulation of innate immunity. Previous studies showed that Fps/Fes-knockout mice were hypersensitive to systemic lipopolysaccharide (LPS) challenge, and Fer-deficient mice displayed enhanced recruitment of leucocytes in response to localized LPS challenge. We show here for the first time, a role for Fps in the regulation of leucocyte recruitment to areas of inflammation. Using the cremaster muscle intravital microscopy model, we observed increased leucocyte adherence to venules, and increased rates and degrees of transendothelial migration in Fps/Fes-knockout mice relative to wild-type animals subsequent to localized LPS challenge. There was also a decreased vessel wall shear rate in the post-capillary venules of LPS-challenged Fps/Fes-knockout mice, and an increase in neutrophil migration into the peritoneal cavity subsequent to thioglycollate challenge. Using flow cytometry to quantify the expression of surface molecules, we observed prolonged expression of the selectin ligand PSGL-1 on peripheral blood neutrophils from Fps/Fes-knockout mice stimulated ex vivo with LPS. These observations provide important insights into the observed in vivo behaviour of leucocytes in LPS-challenged Fps/Fes-knockout mice and provide evidence that the Fps/Fes kinase plays an important role in the innate immune response. [source] Defining the roles of T cell membrane proteinase and CD44 in type 1 diabetesIUBMB LIFE, Issue 1 2007Alexei Y. Savinov Abstract Membrane type-1 matrix metalloproteinase (MT1-MMP) shedding of the signaling and adhesion CD44 receptor plays a significant role in stimulating cancer cells locomotion. Similarly, and unexpectedly, MT1-MMP-dependent shedding of CD44 plays an equally significant role in regulating the adhesion to the pancreatic vasculature and also in the concomitant transendothelial migration and intra-islet homing of the diabetogenic, cytotoxic, T cells. Inactivation of the T cell MT1-MMP functionality by clinically tested, synthetic inhibitors leads to an extended immobilization of the T killer cells on the pancreatic vasculature and, subsequently, to immunosuppression because of the cessation of the T cell transmigration and homing. Injections of insulin jointly with an MT1-MMP inhibitor stimulated the regeneration of functional, insulin-producing, ,-cells in acutely diseased non-obese diabetic (NOD) mice. After insulin injections were suspended and inhibitor injections continued, diabetic NOD mice maintained mild hyperglycemia and did not require further insulin injections for survival. Overall, these data provide a substantive mechanistic rationale for clinical trials of the inhibitors of MT1-MMP in human type 1 diabetes. IUBMB Life, 59: 6-13, 2007 [source] Increased Sensitivity to the C-X-C Chemokine CINC/gro in a Model of Chronic InflammationMICROCIRCULATION, Issue 2 2000Brent Johnston ABSTRACT Objective: The C-C chemokine MCP-1 elicits significant neutrophil emigration in rats with chronic adjuvant-induced inflammation, but not in naive animals. We examined responses to the C-X-C chemokine CINC/gro to determine whether this class of chemokine elicits altered neutrophil responses during chronic inflammation. Methods: CINC/gro was superfused over mesenteric venules of naive rats or animals with chronic adjuvant-induced vasculitis. Antibodies were used to characterize adhesive mechanisms. Results: CINC/gro elicited leukocyte transendothelial migration in adjuvantimmunized rats at 100-fold lower concentrations than required to elicit transmigration in naive animals. In both groups, neutrophils constituted >95% of the leukocytes recruited by CINC/gro. Using in vitro chemotaxis assays, neutrophils from control and adjuvant-immunized rats responded equally to CINC/gro, suggesting differences in migration were not related to neutrophil phenotype. Differences in adhesion molecule usage were noted in vivo. In control animals, CD18 antibodies blocked CINC/gro-induced neutrophil adhesion and emigration. In adjuvant-immunized animals, an ,4 -integrin antibody reduced adhesion and emigration, while a CD18 antibody selectively inhibited emigration. Conclusions: This study demonstrates increased sensitivity to a C-X-C chemokine in a model of chronic inflammation, implicates the ,4 -integrin in neutrophil adhesion, and demonstrates that CD18 mediates leukocyte transendothelial migration independent from firm adhesion. [source] Nitric oxide modulation of low-density mononuclear cell transendothelial migrationMICROSURGERY, Issue 5 2005J.S. Isenberg M.D., M.P.H. The blood-endothelial cell interface is a region of significant importance in many physiologic and pathologic processes. Blood-borne macromolecules and cells gain access to the subendothelial space and extravascular tissues by traversing the endothelium. Yet the various factors responsible for modulation of this process remain only partially elucidated. Several agents were found to be involved in this process, including nitric oxide (NO) and vascular endothelial growth factor (VEGF). It is known that under stress conditions (e.g., inflammation), NO can modulate the permeability of endothelial-cell monolayers to low-density mononuclear cells (LDMNCs). However, it is not known if NO can modulate such effects in the absence of inflammatory stimulation. In the present study, we utilized a Transwell chamber model to examine endothelial-cell monolayer permeability to LDMNCs in the absence of inflammatory stimuli. We noted that NO donor and L-arginine increased transendothelial-cell migration, whereas nitric oxide synthase (NOS) inhibition decreased migration. These effects were not significantly abrogated by VEGF antibody, suggesting that they were not VEGF-dependent. © 2005 Wiley-Liss, Inc. Microsurgery 25:452,456, 2005. [source] Tannerella forsythia infection-induced calvarial bone and soft tissue transcriptional profilesMOLECULAR ORAL MICROBIOLOGY, Issue 5 2010V. Bakthavatchalu Summary Tannerella forsythia is associated with subgingival biofilms in adult periodontitis, although the molecular mechanisms contributing to chronic inflammation and loss of periodontal bone remain unclear. We examined changes in the host transcriptional profiles during a T. forsythia infection using a murine calvarial model of inflammation and bone resorption. Tannerella forsythia was injected into the subcutaneous soft tissue over calvariae of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated and Murine GeneChip® (Affymetrix, Santa Clara, CA) array analysis of transcript profiles showed that 3226 genes were differentially expressed in the infected soft tissues (P < 0.05) and 2586 genes were differentially transcribed in calvarial bones after infection. Quantitative real-time reverse transcription-polymerase chain reaction analysis of transcription levels of selected genes corresponded well with the microarray results. Biological pathways significantly impacted by T. forsythia infection in calvarial bone and soft tissue included leukocyte transendothelial migration, cell adhesion molecules (immune system), extracellular matrix,receptor interaction, adherens junction, and antigen processing and presentation. Histologic examination revealed intense inflammation and increased osteoclasts in calvariae compared with controls. In conclusion, localized T. forsythia infection differentially induces transcription of a broad array of host genes, and the profiles differ between inflamed soft tissues and calvarial bone. [source] Molecular characterization of Treponema denticola infection-induced bone and soft tissue transcriptional profilesMOLECULAR ORAL MICROBIOLOGY, Issue 4 2010V. Bakthavatchalu Summary Treponema denticola is associated with subgingival biofilms in adult periodontitis and with acute necrotizing ulcerative gingivitis. However, the molecular mechanisms by which T. denticola impacts periodontal inflammation and alveolar bone resorption remain unclear. Here, we examined changes in the host transcriptional profiles during a T. denticola infection using a murine calvarial model of inflammation and bone resorption. T. denticola was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and the calvarial bones were excised. RNA was isolated and analysed for transcript profiling using Murine GeneChip® arrays. Following T. denticola infection, 2905 and 1234 genes in the infected calvarial bones and soft tissues, respectively, were differentially expressed (P , 0.05). Biological pathways significantly impacted by T. denticola infection in calvarial bone and calvarial tissue included leukocyte transendothelial migration, cell adhesion (immune system) molecules, cell cycle, extracellular matrix,receptor interaction, focal adhesion, B-cell receptor signaling and transforming growth factor-, signaling pathways resulting in proinflammatory, chemotactic effects, and T-cell stimulation. In conclusion, localized T. denticola infection differentially induces transcription of a broad array of host genes, the profiles of which differed between inflamed calvarial bone and soft tissues. [source] Endothelial Cell Calpain Activity Facilitates Lymphocyte DiapedesisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2005Amer M. Hussain Lymphocyte infiltration of tissue is a cardinal feature of solid-organ allograft rejection. Vascular endothelial cells (EC) participate in lymphocyte recruitment through the display of adhesion molecules and chemokines to promote leukocyte extravasation. Moreover, EC reorganize the cytoskeleton and cytoskeleton-associated structures during leukocyte diapedesis. We examined the role of EC (Ca+2)i and the calcium-sensitive protease, calpain, during lymphocyte diapedesis through a human EC monolayer under physiologic shear stress in vitro. We observed that lymphocyte transendothelial migration (TEM) was inhibited by chelating EC cytosolic calcium, or depleting EC endoplasmic reticulum calcium stores by inhibition of the endoplasmic reticulum Ca ATPase. Further, inhibition of EC phospholiase C also decreased lymphocyte TEM. We determined that EC constitutively exhibit calpain activity, using fluorescence generation from a calpain substrate to report calpain activity in individual live cells. Moreover, EC adjacent to a transmigrating lymphocyte showed increased calpain activity. Further, lymphocyte TEM was inhibited by agents that block calpain activity. Inhibition of lymphocyte TEM occurs at the lumenal EC surface and correlates with impaired development of intercellular adhesion molecule 1 (ICAM-1)-rich docking structures by the EC. We conclude EC calcium and calpain activity facilitates lymphocyte TEM, and participates in the assembly of the docking structure. [source] Junctional adhesion molecule C mediates leukocyte adhesion to rheumatoid arthritis synoviumARTHRITIS & RHEUMATISM, Issue 10 2008Bradley J. Rabquer Objective Leukocyte infiltration into the rheumatoid arthritis (RA) synovium is a multistep process in which leukocytes leave the bloodstream and invade the synovial tissue (ST). Leukocyte transendothelial migration and adhesion to RA ST requires adhesion molecules on the surface of endothelial cells and RA ST fibroblasts. This study was undertaken to investigate the role of junctional adhesion molecule C (JAM-C) in mediating leukocyte recruitment and retention in the RA joint. Methods Immunohistologic analysis was performed on RA, osteoarthritis (OA), and normal ST samples to quantify JAM-C expression. Fibroblast JAM-C expression was also analyzed using Western blotting, cell surface enzyme-linked immunosorbent assay, and immunofluorescence. To determine the role of JAM-C in leukocyte retention in the RA synovium, in vitro and in situ adhesion assays and RA ST fibroblast transmigration assays were performed. Results JAM-C was highly expressed by RA ST lining cells, and its expression was increased in OA ST and RA ST endothelial cells compared with normal ST endothelial cells. JAM-C was also expressed on the surface of OA ST and RA ST fibroblasts. Furthermore, we demonstrated that myeloid U937 cell adhesion to both OA ST and RA ST fibroblasts and to RA ST was dependent on JAM-C. U937 cell migration through an RA ST fibroblast monolayer was enhanced in the presence of neutralizing antibodies against JAM-C. Conclusion Our results highlight the novel role of JAM-C in recruiting and retaining leukocytes in the RA synovium and suggest that targeting JAM-C may be important in combating inflammatory diseases such as RA. [source] Acceleration of the onset of collagen-induced arthritis by a deficiency of platelet endothelial cell adhesion molecule 1ARTHRITIS & RHEUMATISM, Issue 11 2003Yoshifumi Tada Objective Platelet endothelial cell adhesion molecule 1 (PECAM-1; CD31) is a member of the immunoglobulin superfamily that is expressed in platelets, leukocytes, and endothelial cells. PECAM-1 has been shown to play a role in transendothelial migration of leukocytes and contains immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail and inhibits cellular responses. We examined the role of PECAM-1 in the development of collagen-induced arthritis (CIA). Methods CIA was induced in PECAM-1,deficient DBA/1 mice. The incidence of arthritis and the arthritis index were examined. Anti,type II collagen (anti-CII) antibody levels and interferon-, (IFN,) production by lymph node cells and spleen cells were determined. Lymphocytes from arthritic PECAM-1,deficient and wild-type mice were labeled with dye, transferred to arthritic PECAM-1+/, mice, and cell migration to inflamed joints was examined. Results PECAM-1,deficient mice showed accelerated onset of arthritis and increased severity only during the early phase. Anti-CII antibody levels were also increased during the early phase. IFN, production by lymph node cells and spleen cells from PECAM-1,deficient mice in response to CII was higher than that in wild-type mice. Lymphocytes from arthritic PECAM-1,deficient mice showed accelerated migration to inflamed joints, but not lymph nodes or spleen. The development of anti-CII antibody,induced arthritis was similar in PECAM-1,deficient and wild-type mice. Conclusion These results indicate that PECAM-1 negatively regulates humoral and cell-mediated immune responses and lymphocyte migration into joints and, consequently, the development of CIA. In addition, the role of PECAM-1 in the transendothelial migration of leukocytes appears to be redundant in this model. [source] Functional response of leukaemic blasts to stromal cell-derived factor-1 correlates with preferential expression of the chemokine receptor CXCR4 in acute myelomonocytic and lymphoblastic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2000Robert Möhle The chemokine stromal cell-derived factor-1 (SDF-1) that is released by bone marrow (BM) stromal cells and contributes to stem cell homing may also play a role in the trafficking of leukaemic cells. We analysed SDF-1-induced intracellular calcium fluxes in leukaemic blasts from the peripheral blood of patients with newly diagnosed acute myeloid leukaemia (AML) and lymphoblastic leukaemia (B-lineage ALL), determined the effect of BM stromal cell-conditioned medium on in vitro transendothelial migration (TM) and measured expression of the SDF-1 receptor, CXCR4, by flow cytometry. AML FAB M1/2 blasts did not show calcium fluxes and TM was not stimulated. In myelomonocytic AML (M4/5), however, SDF-1 induced significant calcium fluxes and TM was increased twofold by the conditioned medium. M3 and M4 blasts with eosinophilia (M4eo) showed intermediate activity and M6 blasts showed no functional activity. In ALL, strong calcium fluxes and increased TM (2.5-fold) were observed. Accordingly, expression of CXCR4 was low in undifferentiated (M0) AML, myeloid (M1/2) AML and erythroid (M6) AML, but high [mean fluorescence (MF) > 50] in promyelocytic (M3) AML, myelomonocytic (M4/5) AML and B-lineage ALL. We conclude that, in AML, SDF-1 is preferentially active in myelomonocytic blasts as a result of differentiation-related expression of CXCR4. Functional activity of SDF-1 and high expression of CXCR4 in B-lineage ALL is in accordance with the previously described activity of SDF-1 in early B cells. SDF-1 may contribute to leukaemic marrow infiltration, as suggested by increased CXCR4 expression and migratory response in BM-derived blasts compared with circulating cells. [source] Effects of pentoxifylline on the different steps during adhesion and transendothelial migration of flowing neutrophilsCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2001P.S. Bahra Abstract We used a flow system to observe the stepwise adhesion and migration of neutrophils on cultured human umbilical vein endothelial cells (HUVEC) stimulated with tumour necrosis factor-, (TNF) for 4,h, and to evaluate the effects of pentoxifylline (PTX) at each step. When HUVEC had been stimulated with 100,U,ml,1 TNF, treatment of neutrophils with PTX did not reduce the number captured from flow but did cause nearly all adherent cells (,>,90%) to roll, whereas most untreated cells became immobilized and ,30% transmigrated within minutes. On washout of the PTX, many rolling cells halted and started to migrate. Treatment of the HUVEC with PTX at the same time as 100,U,ml,1 TNF did not affect the number of neutrophils adhering, but there was a significant increase in the percentage of cells rolling even though PTX was no longer present. Thus PTX reduced presentation of activating agents by HUVEC, as well as inhibiting the response by neutrophils to surface-presented activating agent(s). If HUVEC were stimulated with 10,U,ml,1 TNF with PTX, the adhesion of flowing neutrophils was greatly inhibited compared to TNF alone. Surface ELISA indicated that PTX reduced TNF-induced upregulation of E-selectin. This reduction was only sufficient to reduce capture of neutrophils at the low dose of TNF. Thus, by using a flow-based model, we have been able to separate the effects of a multipotent agent such as pentoxifylline, which acts on leucocytes and endothelial cells, at each stage of migration. Copyright © 2001 John Wiley & Sons, Ltd. [source] | |||||||||||||