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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recirculation of mouse lymphocytes to the gut involves binding of the lymphocyte integrin alpha 4 beta 7 to the mucosal vascular addressin, MAdCAM-1. In humans, indirect evidence suggests that CD4+ T cells that express high levels of alpha 4 beta 7 migrate selectively to the gut. We now report that human adult blood CD8+ T cells and B cells, like CD4+ T cells, have heterogeneous expression of alpha 4 beta 7. In contrast, NK cells, eosinophils, and newborn blood T and B cells have relatively homogeneous expression of alpha 4 beta 7. CD4+ and CD8+ T cell expression of alpha 4 beta 7 was related to age, CD45RA expression, and integrin beta 1 (CD29) expression, suggesting that alpha 4 beta 7 expression changes after primary activation of CD4+ and CD8+ T cells in vivo. To directly determine whether human alpha 4 beta 7 mediates adhesion to MAdCAM-1, we performed in vitro adhesion assays with two alpha 4 beta 7+ human lymphoma cell lines. The results indicate that human alpha 4 beta 7 is a receptor for MAdCAM-1, whereas alpha 4 beta 1 is not. Adhesion of HUT 78 cells to MAdCAM-1 required Mn2+, whereas adhesion of RPMI 8866 cells did not, suggesting that alpha 4 beta 7 may have at least two distinct functional states. The ability of lymphocytes to bind to MAdCAM-1 and recirculate to mucosal organs is likely to be influenced both by the level of alpha 4 beta 7 expression and by the functional state of the alpha 4 beta 7 molecule.
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PMID:Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes. 751 18

Several chemoattractant receptors can support agonist-induced, integrin-dependent arrest of rolling neutrophils in inflamed venules in vivo, as well as subsequent crawling into tissues. It has been hypothesized that receptors of the Galpha(i)-linked chemoattractant subfamilies, especially receptors for chemokines, may mediate parallel activation-dependent arrest of homing lymphocyte subsets. However, although several chemokines can attract subsets of B or T cells, robust chemoattractant triggering of resting lymphocyte adhesion to vascular ligands has not been observed. To study the biology of individual leukocyte chemoattractant receptors in a defined lymphoid environment, mouse L1/2 pre-B cells and/or human Jurkat T cells were transfected with alpha (IL-8 receptor A) or beta (MIP-1alpha/CC-CKR-1) chemokine receptors, or with the classical chemoattractant C5a (C5aR) or formyl peptide receptors (fPR). All receptors supported robust agonist-dependent alpha4beta1 integrin-mediated adhesion of lymphocytes to VCAM-1. L1/2 cells cotransfected with fPR and beta7 integrin were also induced to bind MAdCAM-1, suggesting common mechanisms coupling chemoattractant receptors to activation of distinct integrins. Adhesion was rapid but transient, with spontaneous reversion to unstimulated levels within 5 min after peak binding. When observed under flow conditions, alpha4beta1-mediated arrest occurred within seconds after initiation of contact and rolling of IL-8RA transfectants on VCAM-1/IL-8 co-coated surface; and arrest reversed spontaneously after a mean of 5 min with a return to rolling behavior. Each of the receptors also conferred agonist-specific chemotaxis; however, whereas strong adhesion required simultaneous occupancy of many receptors with maximal responses above the Kd, chemotaxis in each case was suppressed at high agonist concentrations. The findings indicate that alpha and beta chemokine as well as classical chemoattractant receptors can trigger robust adhesion as well as directed migration of lymphoid cells, but that the requirements for and kinetics of adhesion triggering and chemotaxis are distinct, thus permitting their independent regulation. They suggest that the discordance between proadhesive and chemoattractant responses of circulating lymphocytes to many chemokines may reflect quantitative aspects of receptor expression and/or coupling rather than qualitative differences in receptor signaling.
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PMID:Biology of chemokine and classical chemoattractant receptors: differential requirements for adhesion-triggering versus chemotactic responses in lymphoid cells. 869 20

Ligands on human basophils for the endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), mucosal addressin cell adhesion molecule-1 (MAdCAM-1), and E-selectin were investigated. Adhesion of basophils to endothelial cells was inhibited by mAb recognizing CD18, CD11a, and/or CD11b, with the pattern and magnitude of inhibition dependent upon the activation state of the basophils and endothelium. Adhesion to recombinant VCAM-1 was completely inhibited by mAb recognizing alpha 4 integrin and partially by mAb to the beta 1 or beta 7 subunit; surface expression of these integrins was also detected. Adhesion to recombinant MAdCAM-1 expressed on Chinese hamster ovary cells was completely inhibited by mAb recognizing alpha 4 and/or beta 7 integrins. Adhesion to recombinant E-selectin was completely inhibited by basophil pretreatment with neuraminidase and partially inhibited by endo-beta-galactosidase. By flow cytometry, bimodal patterns of expression of sialyl-Lewis X- and sialyl-dimeric-Lewis X were observed, and adherent cells tended to be sialyl-dimeric-Lewis X positive. Thus, basophils express beta 1, beta 2, and beta 7 integrins along with sialylated surface ligands that may interact with the endothelium during basophil recruitment responses.
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PMID:Counter-receptors on human basophils for endothelial cell adhesion molecules. 875 37

This article reviews the molecular basis of cell adhesion and its possible implications in surgery. Adhesion of circulating cells to endothelial cells is mediated by a variety of celladhesion molecules. The first steps in the cell adhesion cascade (rolling, tethering) are regulated by selectins (P, E, L selectin). Stable adhesion and transmural migration predominantly involve integrins (LFA-1, etc.) and members of the immunoglobulin supergene family (ICAM-1, etc). The mechanisms of leucocyte-endothelial interaction are markedly similar in various organs under both physiological and pathophysiological conditions. However, it is likely that cell trafficking to specific tissues/organs (e.g., homing) is regulated by additional organ-specific, topical adhesion molecules (e.g., MAdCAM-1). In surgery, cell adhesion molecules are involved in organ-transplantation pathology (ischemia/reperfusion injury, rejection), inflammation (e.g., chronic inflammatory bowel diseases), tumor metastasis. Animal experiments with anti-adhesive substances show that blocking the leukocyte-endothelial interaction reduces the cellular inflammatory infiltrate and organ rejection. The transfer of experimental data into clinical practice requires further understanding of the regulators of cell adhesion (cytokines, chemoattractant substances, etc.) and the specificity of the process. Current experimental data suggest that early intervention in cell-adhesion mechanisms may offer innovative therapeutic strategies.
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PMID:[Cell adhesion. Molecular principles and initial implications for surgery]. 930 36

Adhesion of blood leukocytes to the endothelium involves multiple steps including initial attachment (tethering), rolling, and firm arrest. Presentation of adhesion molecules on leukocyte microvilli can substantially enhance tethering. Localization of L-selectin to microvilli and of CD44 to the planar cell body have been shown to depend upon their transmembrane and cytoplasmic domains. We investigated the role of leukocyte integrin transmembrane and cytoplasmic domains in initiating adhesion under flow and in microvillous localization. Integrins alpha4beta7, alphaLbeta2, and alphaMbeta2 were heterologously expressed in K562 cells. alpha4beta7 initiated adhesion under flow and localized to microvilli, whereas beta2 integrins did not initiate adhesion and localized to the cell body. Chimeric integrins were produced by replacing the alpha4beta7 cytoplasmic and/or transmembrane domains with the homologous domains of alphaLbeta2 or alphaMbeta2. Unexpectedly, these chimeras efficiently mediated adhesion to the alpha4beta7 ligand mucosal addressin cell adhesion molecule-1 under flow and localized to microvilli. Therefore, differences between the transmembrane and cytoplasmic domains of alpha4 and beta2 integrins do not account for differences in ability to support attachment under flow or in membrane localization. Integrins alpha4beta1, alpha5beta1, alpha6Abeta1, alphavbeta3, and alphaEbeta7 also localized to microvilli. Transmembrane proteins known or suspected to associate with extracellular domains of microvillous integrins, including tetraspans and CD47, were concentrated on microvilli as well. These findings suggest that interactions between the extracellular domains of integrins and associated proteins could direct the assembly of multimolecular complexes on leukocyte microvilli.
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PMID:Presentation of integrins on leukocyte microvilli: a role for the extracellular domain in determining membrane localization. 933 57

Migration of blood-borne lymphocytes into lymphoid tissues is initiated by the L-selectin and alpha4beta7 integrin adhesion molecules. Previous studies have shown that L-selectin adhesion is dynamically regulated by febrile temperatures. It is now reported that fever-range hyperthermia also acts directly on lymphocytes to enhance selected adhesive functions of alpha4beta7 integrin. Fever-range hyperthermia treatment in vitro (40 degrees C, 12 h) of murine TK1 lymphoma cells and human peripheral blood lymphocytes (PBL) stimulates alpha4beta7 integrin-dependent adhesion to high endothelial venules (HEV) in Peyer's patch and mesenteric lymph node frozen sections. TK1 cells are alpha4beta7hi L-selectin(lo), allowing for the analysis of alpha4beta7 integrin without contributions from L-selectin. Adhesion was further shown to involve alpha4beta7 integrin and its endothelial counter-receptor, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) using function-blocking antibodies (i.e. DATK32, HP2/1, MECA-367). Fever-range hyperthermia also promotes alpha4beta7 integrin-mediated aggregation of TK1 cells. In sharp contrast, hyperthermia fails to increase alpha4beta7 integrin adhesion to fibronectin by TK1 cells. Expression of the alpha4beta7 heterodimer on TK1 cells or human PBL is not altered by hyperthermia, suggesting that hyperthermia stimulates adhesion by enhancing alpha4beta7 integrin avidity rather than its cell surface density. These results provide a mechanism whereby febrile temperatures during infection or clinical hyperthermia potentially amplify the immune response by stimulating L-selectin and alpha4beta7 integrin-dependent homing of immune effector cells to lymphoid tissues.
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PMID:Fever-range hyperthermia stimulates alpha4beta7 integrin-dependent lymphocyte-endothelial adhesion. 1066 16

Adhesion and stabilization of circulating tumor cells to endothelial cells in target blood vessels play an important role in the complex process of metastasis. We examined the cell surface receptors involved in the liver-metastatic adhesive interactions of murine RAW117 large-cell lymphoma cells to unstimulated hepatic sinusoidal endothelial cells (HSE) under physiological flow conditions. Flow cytometric analysis indicated that VCAM-1, ICAM-1 and PECAM-1 are constitutively expressed on the surfaces of both HSE and RAW117 cells. However, monoclonal antibody (mAb) blockade studies showed that ICAM-1 and PECAM-1 affected neither the attachment nor the stabilization step of the adhesion of RAW117 cells to HSE cell monolayers under flow. In contrast, RAW117 cells required a significantly lower shear stress to establish adhesion to HSE cells when VCAM-1 receptors on HSE cells were blocked with mAb. Furthermore, the presence of the anti-VCAM-1 mAb significantly decreased the extent of adhesion compared to that of the control, without affecting adherent cell stabilization times. Blocking the alpha4 integrin subunits present mainly on RAW117 cells produced similar results to those previously observed with anti-VCAM-1 mAb. Although constitutively present mainly on the surfaces of RAW117 cells, MAdCAM-1 and beta7 integrin subunit do not appear to play a role in either the arrest or stabilization of RAW117 cells on HSE cell monolayers. However, blocking the beta1 integrin subunit on the RAW117-H10 cells reduced adhesion to the same extent as anti-alpha4 and anti-VCAM-1 treatments. These observations suggest that an interaction of integrin alpha4/beta1 on RAW117 cells with liver endothelial VCAM-1 occurs during the early stages of the adhesion process and may be important in liver metastasis.
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PMID:Integrin alpha4beta1/VCAM-1 pathway mediates primary adhesion of RAW117 lymphoma cells to hepatic sinusoidal endothelial cells under flow. 1091 12

Adhesion molecule immunoneutralization is envisioned as a promising therapy for inflammatory bowel disease, but the relative value of selective blockade of different adhesion molecules has not been established. The aims of this study were to measure expression and functional relevance of endothelial intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in leukocyte recruitment in experimental colitis and to compare the therapeutic effectiveness of their selective blockade. For this purpose, cell adhesion molecule expression was measured by the dual radiolabeled antibody technique in mice with dextran sulfate sodium-induced colitis and controls. Leukocyte-endothelial cell interactions were determined in colonic venules by fluorescence intravital microscopy. Therapeutic effects of chronic treatment with anti-ICAM-1, anti-VCAM-1, or anti-MAdCAM-1 antibodies were also assessed. Whereas colonic endothelial ICAM-1 was constitutively expressed and had a mild up-regulation in colitic animals, constitutive expression of VCAM-1 and MAdCAM-1 was low, but markedly increased after induction of colitis. Leukocyte adhesion was abrogated by immunoneutralization of VCAM-1 or MAdCAM-1 but not by treatment with an anti-ICAM-1 antibody. Chronic administration of anti-VCAM-1 antibody, but not anti-ICAM-1 or anti-MAdCAM-1, resulted in significant attenuation of colitis in terms of disease activity index, colon length, ratio of colon weight to length, and myeloperoxidase activity. In conclusion, VCAM-1 plays a central role in leukocyte recruitment in colitis and blockade of this adhesion molecule has higher therapeutic effect than immunoneutralization of ICAM-1 or MAdCAM-1 in this experimental model.
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PMID:VCAM-1, but not ICAM-1 or MAdCAM-1, immunoblockade ameliorates DSS-induced colitis in mice. 1104 71

The development of a protective vaccine against the sexually transmitted disease caused by Chlamydia trachomatis may prevent complications associated with insidious infection. Vaccination via the vaginal route may not be practical, and other routes should be investigated. To this end, the adhesion molecules induced on the fallopian tube endothelium during infection with C. trachomatis were characterized. Adhesion molecules were identified in fallopian tube biopsy specimens cultured with 5 x 10(6) infection-forming units of C. trachomatis serovar E. Frozen sections were prepared from these tissues and were stained by immunohistochemical techniques. Infection with live, but not UV-inactivated, C. trachomatis induced a significant increase in levels of vascular cell adhesion molecule-1 and the mucosal addressin cell adhesion molecule-1 but not of other adhesion molecules. Therefore, infection with C. trachomatis induces adhesion molecules that are associated with other mucosal tissues and inflammatory sites, which suggests that mucosal routes of immunization may be effective.
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PMID:Chlamydia trachomatis infection induces mucosal addressin cell adhesion molecule-1 and vascular cell adhesion molecule-1, providing an immunologic link between the fallopian tube and other mucosal tissues. 1155 Jan 28

Precursors of uterine NK cells home to the uterus during early pregnancy from multiple lymphohemopoietic sources. In mouse uterine tissue, pregnancy markedly up-regulates both L-selectin- and alpha(4) integrin-dependent adhesion pathways for circulating human CD56(bright) cells, the phenotype of human uterine NK cells. Based on roles for these adhesion molecules in lymphocyte homing, we examined effects of pregnancy or the steroid hormones 17beta-estradiol or progesterone on lymphocyte-endothelial interactions in secondary lymphoid tissues and in uterus. From preimplantation gestation day 3, specialized high endothelial venules in peripheral lymph nodes and Peyer's patches supported elevated L-selectin and alpha(4)beta(7) integrin-dependent lymphocyte adhesion under shear throughout pregnancy, as compared with high endothelial venules of virgin or postpartum donors. Squamous endothelium from nonlymphoid tissue was not affected. Pregnancy-equivalent endothelial responses were observed in lymph nodes and Peyer's patches from ovariectomized mice receiving 17beta-estradiol and/or progesterone replacement therapy. Adhesion of human CD56(bright) cells to uteri from pregnant or hormone-treated ovariectomized mice was enhanced through L-selectin- and alpha(4) integrin-dependent mechanisms and involved multiple vascular adhesion molecules including mucosal addressin cell adhesion molecule-1, VCAM-1, and peripheral lymph node addressin. Analysis of Tie2-green fluorescence protein transgenic mice demonstrated that CD56(bright) cells adhered primarily to vascular endothelium within the decidua basalis. Microdomain localization of adhesion involving large clusters of lymphocytes was induced on uteri from natural matings, but not pseudopregnancy. Steroid hormones also had independent effects on L-selectin function in splenic lymphocytes that mimicked physiological stimulation induced by pregnancy or fever-range temperatures. These results provide the first evidence for coordinated, organ-specific, steroid hormone-induced changes in lymphocyte homing mechanisms that could contribute to local and systemic immune responses during pregnancy.
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PMID:Coordinate regulation of lymphocyte-endothelial interactions by pregnancy-associated hormones. 1453 Mar 21


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