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PubMed2005

Bifunctional peptides derived from homologous loop regions in the laminin alpha chain LG4 modules interact with both alpha 2 beta 1 integrin and syndecan-2.

Laminin alpha chains show diverse biological functions in a chain-specific fashion. The laminin G-like modules (LG modules) of the laminin alpha chains consist of a 14-stranded beta-sheet sandwich structure with biologically active sequences found in the connecting loops. Previously, we reported that connecting loop regions between beta-strands E and F in the mouse laminin alpha chain LG4 modules exhibited chain-specific activities. In this study, we focus on the homologous loop regions in human laminin alpha chain LG4 modules using five synthetic peptides (hEF-1-hEF-5). These homologous peptides induced chain-specific cellular responses in various cell types. Next, to examine the dual-receptor recognition model, we synthesized chimeras (cEF13A-cEF13E) derived from peptides hEF-1 and hEF-3. All of the chimeric peptides promoted fibroblast attachment as well as the parental peptides. Attachment of fibroblasts to cEF13A and cEF13B was inhibited by anti-integrin alpha2 and beta1 antibodies and by heparin, while cell adhesion to cEF13C, cEF13D, and cEF13E was blocked only by heparin. Actin organization of fibroblasts on cEF13C was not different from that on hEF-3, but cEF13B induced membrane ruffling at the tips of the actin stress fibers. These results suggest that cEF13B had bifunctional effects on cellular behaviors through alpha2beta1 integrin and heparin/heparan sulfate proteoglycan. We conclude that the approach utilizing chimeric peptides is useful for examining cellular mechanisms in dual-receptor systems.

Actins↗
PubMed1993

Integrin receptors and function on cultured glomerular endothelial cells.

Integrin expression and function on a cloned line of rat glomerular endothelial cells (GEndoC) were studied in an effort to obtain a better understanding of the means by which these cells interact with components of the glomerular basement membrane. Cultured GEndoC adhered to fibronectin, laminin and types I and IV collagen and expressed alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha v beta 1 and alpha v beta 3 integrins. Synthetic RGDS peptides significantly decreased adhesion to fibronectin (53.1 +/- 4.7% of control). Antibody to rat beta 1 integrin strongly inhibited adhesion to laminin, fibronectin and types I and IV collagen (11.2, 19.0, 67.3 and 31.9% of control adhesion, respectively), while antibody to the rat alpha 1 integrin chain strongly inhibited adhesion to laminin (65.2% of control), but only mildly inhibited adhesion to type IV collagen (77.2% of control) and did not affect adhesion to type I collagen (97.8% of control). Affinity chromatography of GEndoC lysates on a column of immobilized type I collagen displayed predominantly binding of alpha 3 beta 1 integrin with trace amounts of alpha 1 beta 1 and alpha 2 beta 1, documenting the major role of alpha 3 beta 1 in GEndoC adhesion to collagen. Chromatography on the immobilized cell-binding fragment of fibronectin revealed the alpha 5 beta 1 integrin to be the major fibronectin receptor on these cells, but antibody to alpha v beta 3 integrin also documented a minor role for alpha v beta 1 or alpha v beta 3 in fibronectin adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Immunohistochemical localization of beta 1-integrins in anterior cruciate and medial collateral ligaments of human and rabbit.

The integrins are a family of adhesion-mediating cell surface receptors that play critical roles in cell-extracellular matrix interactions and have been shown to be important in the healing response in several tissues. We have studied integrin expression in normal human and rabbit anterior cruciate (ACL) and medial collateral (MCL) ligaments of the knee as a preamble to studies of beta 1-integrin expression in healing ligaments. Histologic sections of human and rabbit ACL and MCL were probed for integrin expression utilizing integrin-specific monoclonal antibodies (mAbs) followed by immunoperoxidase detection. Staining of human specimens with mAbs revealed the presence of beta 1-, alpha 1-, and alpha 5-integrin chains on the tissue fibroblasts of both ACL and MCL, while staining of rabbit specimens with rabbit integrin-reactive monoclonals revealed the presence of beta 1- and alpha 5-integrin on these ligaments. Equivalent amounts of the integrins studied were present on normal ACL and MCL. We conclude that the rabbit is an appropriate model for analyzing the expression and functional role of integrins in ligament wound healing.

Animals↗
PubMed1989

Peyer's patch-specific lymphocyte homing receptors consist of a VLA-4-like alpha chain associated with either of two integrin beta chains, one of which is novel.

Lymphocytes home to various lymphoid organs by adhering to and migrating through specialized high endothelial venules (HEV). The murine cell surface heterodimer LPAM-1 is involved in the homing of lymphocytes to mucosal sites (Peyer's patches). LPAM-1 has an alpha subunit (alpha 4m) analogous to the alpha chain of the human integrin molecule VLA-4. Here we show that the LPAM-1 beta subunit (beta p) is immunochemically and biochemically distinct from previously defined integrin beta subunits, suggesting that beta p represents a novel integrin beta subunit. Depending on the cellular source two alternative beta subunits, beta p and integrin beta 1, can be isolated in association with alpha 4m. Therefore, alpha 4m is the common subunit of the unique integrin LPAM-1 (alpha 4m beta p) and of the heterodimer LPAM-2 (alpha 4m beta 1), which is analogous to VLA-4. Antibody-blocking experiments suggest that, in addition to LPAM-1, LPAM-2 is also involved in the organ-specific adhesion of lymphocytes to Peyer's patch HEV.

Animals↗
PubMedDate not supplied

[Isolation of a cellular receptor for tick-borne encephalitis virus using anti-idiotypic antibodies].

Cell surface receptors for tick-borne encephalitis (TBE) virus are proposed to be identified by affinity chromatography with polyclonal antiidiotypic antibodies (AIA) as antireceptor antibodies. A single affinity chromatography procedure permitted us to obtain 33-150 times purified cell surface receptor from human embryonic renal cell membranes. Four polypeptides with molecular weight 43, 67, 110, and 210 kD were detected in highly purified fractions of TBE virus cell surface receptor. Antireceptor antibodies reacted in immunoblotting only with the 67 kD polypeptide. The molecular weight of protein p67 suggests that it is the nonintegrin laminin receptor. Monoclonal antibodies 8E3 to beta 1-chain of human integrin and M-KID2 to alpha 3 beta 1-integrin reacted in enzyme immunoassay and spot analysis with purified cell surface receptor for TBE virus. The molecular weight of beta 1-chain of human integrin is 110 kD. Probably, the 210 kD polypeptide is an alpha 3-chain of human integrin. Laminin serves as the ligand for alpha 3 beta 1-integrin and laminin receptor, which can be the structural basis for joint isolation of these molecules from lysates of RH cell membranes in a column with immobilized antireceptor antibodies. The role of p43 protein is not clear. Identification of two laminin-binding protein molecules by means of antireceptor antibodies permits us to propose that laminin-binding sites of human alpha 3 beta 1-integrin and laminin receptor can ensure the receptor interactions between TBE virions and RH cells.

Animals↗
PubMed1992

Diminished expression of integrin adhesion molecules on human colonic epithelial cells during the benign to malign tumour transformation.

Integrins are transmembrane molecules that mediate cell-cell and cell-substratum adhesion. Because alterations in the adhesive properties of tumour cells are thought to influence tumour cell invasion, the expression of integrin alpha and beta chains in 19 human colorectal carcinomas, eight adenomas, and eight normal colon tissues was examined immunohistochemically using an indirect immunofluorescent technique. Normal colonic epithelial cells were found to express the integrin alpha 3, alpha 5, alpha 6, beta 1, and beta 4 chains, whereas the alpha 2 chain was expressed only on epithelial cells lining the base of the crypts and was absent from cells lining the mouth of the crypts or the surface epithelium. No epithelial staining of the alpha 1, alpha 4, beta 2, and beta 3 chains was observed. A progressive reduction of all normally expressed alpha and beta chains was associated with increasing neoplastic transformation. The expression of the alpha 3 and alpha 5 chains was already noticeably reduced in adenomas, and was completely absent in most colonic carcinomas. In contrast, alpha 6, beta 1, and beta 4 expression was maintained in adenomas, whereas the transformation from benign to malignant neoplasms associated with infiltrative growth was characterised by diminished or lost expression of alpha 6, beta 1, and beta 4 chains. Thus, the decreased expression of integrins in human colon carcinomas may contribute to the altered adhesion and migration properties of these tumour cells.

Adenocarcinoma↗
PubMed1993

Structural analysis of the CD11b gene and phylogenetic analysis of the alpha-integrin gene family demonstrate remarkable conservation of genomic organization and suggest early diversification during evolution.

CD11b is a member of the beta 2 subfamily of the human leukocyte integrins. Its expression is limited to mature myeloid and NK cells and is up-regulated during the course of granulocytic and monocytic differentiation. The CD11b/CD18 (Mo1) heterodimer promotes adhesion of granulocytes and monocytes to C3bi-coated bacteria and endothelial cells. In an attempt to relate the exon structure to the known functional domains, as well as to identify and study cis-acting elements that are involved in its tissue-specific expression, we have isolated genomic clones encoding CD11b, deduced the exon/intron organization, and determined the transcriptional start site. The CD11b gene spans 55 kb and is encoded by 30 exons. Its structure closely resembles that of CD11c, another of the three leukocyte integrin alpha-chains, and suggests that these two genes arose by a gene duplication event. Furthermore, comparison of the CD11b gene structure with that of platelet glycoprotein IIb and Drosophila PS2 suggest how the human leukocyte integrins evolved and dispersed during the course of evolution.

Amino Acid Sequence↗
PubMed2003

Preferential accumulation of CD103+ T cells in human livers; its association with extrathymic T cells.

BACKGROUND/AIMS: CD103, a mucosal integrin alphaEbeta7, binds to E-cadherin expressed on hepatocytes and bile duct epithelium in the liver. Although CD103+ T cells are enriched in intestinal intraepithelial lymphocytes, the localization of those cells in the liver is unknown. METHODS: We investigated whether CD103+ cells are present in human livers, and how they are associated with the intrahepatic development of T cells by flow cytometry and immunohistochemistry. RESULTS: Human livers contain significantly (P<0.001) higher percentages of CD103+ cells in CD4+ and CD8+ T cells (25.7+/-13.5 and 27.1+/-19.3%, respectively) than peripheral blood lymphocytes. Moreover, CD103+ cells in the liver, but not in peripheral blood, contained T cells with intermediate expression level of T cell receptor alphabeta. Those cells consist of mostly CD4+ and CD4-CD8- cells, and expressed low level of CD56 and interleukin-2 receptor beta chain in most of the population. These characteristics are distinct from natural killer T cells, which have been thought to be extrathymic T cells in human livers. Moreover, intrahepatic CD103+ cells expressed mRNA for recombination-activating gene-1, -2 and pre T cell receptor-alpha detected by reverse transcription-polymerase chain reaction. CONCLUSIONS: CD103+ T cells are preferentially accumulated in human livers, and those T cells show characteristics of extrathymic T cells.

Antigens, CD↗
PubMed1997

Sequence analysis of rat integrin alpha E1 and alpha E2 subunits: tissue expression reveals phenotypic similarities between intraepithelial lymphocytes and dendritic cells in lymph.

The integrin alpha OX-62 subunit is defined by the OX-62 monoclonal antibody that was raised against rat dendritic cells in lymph (veiled cells) and shows properties similar to those of human alpha E2 that is predominantly expressed on intraepithelial lymphocytes. To clone alpha OX-62, rat probes generated using primers specific for the human alpha E sequence were used to screen rat T cell cDNA libraries. cDNA clones encoding two similar but not identical alpha subunits that are closely related to but distinct from human alpha E were isolated. alpha E1 is predicted to be the rat homolog of mouse alpha M290 and alpha E2 corresponds to rat alpha OX-62. Immunofluorescence analysis revealed that mouse alpha E1 and rat alpha E2 are expressed in dendritic epidermal T cells in the skin, intraepithelial lymphocytes in the small intestine and in cells with a dendritic morphology present at sites where gamma delta T cells occur in lymphoid organs. Unexpectedly, alpha E2 is co-expressed with intracellular CD3-delta and a 33-kDa CD3 chain but not the T cell receptor in veiled cells. These findings suggest that veiled cells may be derived from a lymphoid precursor. Furthermore, veiled cells show phenotypic similarities to intraepithelial lymphocytes.

Amino Acid Sequence↗
PubMed2000

[Effects of fibrinogen, fibrin and their degradation products on the behaviour of vascular smooth muscle cells].

The transition of fibrinogen to fibrin and to their degradation products within the arterial wall has been reported to be accompanied by atherosclerotic progression. A major step in the pathogenesis of atherosclerosis is the vectorial migration of vascular smooth muscle cells (SMCs) from the arterial media through the internal elastic lamina into the intima and their subsequent proliferation in the intima. I have been studying the effects of fibrinogen, fibrin and their degradation products on the behaviour, particularly migration, of SMCs. Fibrinogen/fibrin stimulates the adhesion and migration of SMCs and their effects are mediated by both the RGD-containing region of the alpha chain of fibrinogen/fibrin and integrin alpha v beta 3 on the cell surface. SMCs migrate into fibrin gel even with no other chemotactic stimuli. SMCs displayed two-fold increase in migration into crosslinked fibrin gels compared to non-crosslinked gels, suggesting the importance of fibrin crosslinking by factor XIIIa on its three-dimensional structure for the migration of SMCs. Fibrin gels prepared with batroxobin, which cleaves only fibrinopeptide A, with ACTE, which cleaves only fibrinopeptide B, and with protamine sulfate, which cleaves nothing, but forms a fibrin-like gel, induce migration of SMCs in a manner similar to the gel prepared with thrombin, suggesting that the cleavage of fibrinopeptides is not involved in the migration of SMCs. Both anti-fibrinogen fragment D and E antibodies inhibit the migration of SMCs into fibrin gel, suggesting that both D and E regions of fibrin are involved in the migration of SMCs into fibrin gel. The migration of SMCs into fibrin gel also depends on the RGD-containing region and integrin alpha v beta 3. Both fibrinogen fragments D and E inhibit the migration of SMCs into fibrin gels, suggesting that these fragments may be involved in the regulation of SMC migration into fibrin gel as the result of fibrinolysis. Although subcultured SMCs usually show a synthetic phenotype, the behaviour of contractile SMCs may be crucial for the subsequent migration of the cells. We employed an in vitro assay system to evaluate the effects of fibrin gels on the migration of SMCs from explants taken from rabbit aorta. alpha v beta 3 integrin and the RGD-containing region are involved in the migration of SMCs into the fibrin gels. SMCs which migrated from the explants showed positive staining with monoclonal antibodies against SMC myosin heavy chain isoforms, SMemb, SM1 and SM2, suggesting that they are in an intermediate state changing from a contractile to synthetic state. These findings show that fibrin (ogen) itself induces adhesion and migration of SMCs without other chemotactic or chemokinetic substances, suggesting a crucial role for fibrin (ogen) in the development and progression of such vascular diseases as atherosclerosis, thrombosis and restenosis following balloon angioplasty.

Animals↗
PubMed1995

Molecular mapping of functional antibody binding sites of alpha 4 integrin.

Integrin alpha 4 beta 1 is a leukocyte receptor for fibronectin and vascular cell adhesion molecule-1 (VCAM-1). It is important in inflammatory recruitment of leukocytes, lymphopoiesis, and a number of development events. Here we have mapped a panel of functional monoclonal antibodies (mAbs) recognizing the integrin alpha 4 chain, using murine/human chimeric constructs expressed in COS7 cells. We find that: 1) mAbs that induce homotypic aggregation (epitope A mAbs) map to the most N-terminal 100 amino acids of the human alpha 4 chain; 2) mAbs that block adhesion of alpha 4 beta 1 to VCAM-1 and fibronectin (epitope B mAbs) map to a 52-amino-acid region between residues 152 and 203 of human alpha 4; 3) epitope B mAbs that do or do not induce aggregation (epitope B2 and B1 mAbs, respectively) map to the same regions and are therefore indistinguishable by this analysis; 4) mAbs that neither induce homotypic aggregation nor block adhesion (epitope C mAbs) map to a distinct region of the molecule comprising amino acids 422-606. The N-terminal region of the alpha 4 chain identified by functional A and B epitope mAbs does not correspond to ligand binding sites identified in other alpha subunits, such as cation binding sites or the "I-domain," which alpha 4 lacks, and thus represents a novel site for epitope functionality among the integrins.

Animals↗
PubMed2000

Sequence analysis or rat integrin alphaE1 and alphaE2 subunits: tissue expression reveals phenotypic similarities between intraepithelial lymphocytes and dendritic cells in lymph.

The integrin alphaOX-62 subunit is defined by the OX-62 monoclonal antibody that was raised against rat dendritic cells in lymph (veiled cells) and shows properties similar to those of human alphaE that is predominantly expressed on intraepithelial lymphocytes. To clone alphaOX-62, rat probes generated using primers specific for the human alphaE sequence were used to screen rat T cell cDNA libraries. cDNA clones encoding two similar but not identical alpha subunits that are closely related but distinct from human alphaE were isolated. alphaE1 is predicted to be the rat homolog of mouse alphaM290 and alphaE2 corresponds to rat alphaOX-62. Immunofluorescence analysis revealed that mouse alphaE1 and rat alphaE2 are expressed in dendritic epidermal T cells in the skin, intraepithelial lymphocytes in the small intestine and in cells with a dendritic morphology present at sites where gammadelta T cells occur in lymphoid organs. Unexpectedly, in veiled cells alphaE2 is co-expressed with intracellular CD3-delta and a 33-kDa CD3 chain but not the T cell receptor. These findings suggest that veiled cells may be derived from a lymphoid precursor. Furthermore, veiled cells show phenotypic similarities to intraepithelial lymphocytes.

Amino Acid Sequence↗
PubMed1995

Expression of integrin receptors and ICAM-1 on keratinocytes in vivo and in an in vitro reconstructed epidermis: effect of sodium dodecyl sulphate.

Several integrin heterodimers such as alpha 2 beta 1, alpha 6 beta 4 and alpha v beta 5 are expressed on basal keratinocytes of the epidermis. Because overexpression of these integrins as well as induction of the intercellular adhesion molecule-1 (ICAM-1) have been found in inflammatory dermatoses, we sought to determine whether these modulations could be used as markers of skin irritation. In normal epidermis, topical application of 1% sodium dodecyl sulphate (SDS) for 24 h caused an upregulation of alpha 3, beta 1, alpha 6, beta 4, alpha v, beta 5 and to a lesser extent alpha 2 integrin chains as well as an induction of ICAM-1. To investigate whether these parameters could also be used for evaluation of skin irritancy in vitro, SDS was applied for 24 h to reconstructed epidermis on de-epidermized dermis (RE-DED). In RE-DED, integrin overexpression and aberrant alpha 5 expression was seen under normal in vitro culture conditions and topical application of SDS caused only marginal additional upregulation. We could not detect any ICAM-1 reactivity on either normal or irritated RE-DED. Our results demonstrate that the modulation of integrin and ICAM-1 expression can be used as markers of irritation of the epidermis in vivo, but not in vitro.

Biomarkers↗
PubMed1998

Stimulation of P-selectin glycoprotein ligand-1 on mouse neutrophils activates beta 2-integrin mediated cell attachment to ICAM-1.

The entry of neutrophils into inflamed tissues is initiated by cell rolling on the blood vessel wall followed by arrest and transendothelial migration. Rolling is mediated by the selectins, while the two subsequent steps require activated beta 2-integrins. We have investigated whether the binding of P-selectin to mouse neutrophils could trigger the activation of beta 2-integrins. We show that cross-linking of P-selectin glycoprotein ligand-1 (PSGL-1) on mouse neutrophils with an antibody-like recombinant form of P-selectin or with monoclonal antibodies stimulated the production of reactive oxygen intermediates and enhanced neutrophil attachment to intercellular adhesion molecule 1 (ICAM-1)-expressing CHO cells. This effect was independent of whether complete antibodies or F(ab')2 fragments were used. The adhesion-stimulating effect of P-selectin could be blocked by monoclonal antibodies against PSGL-1. Increase of cell attachment was dependent on lymphocyte function-associated antigen 1 (LFA-1) and on Mac-1, since it could be blocked with antibodies against both respective integrin alpha-chains. Moreover, cell surface expression of Mac-1 increased upon cross-linking of PSGL-1. In agreement with published data, treatment of human neutrophils with P-selectin-IgG did not enhance attachment to ICAM-1. Our data suggest that ligation of PSGL-1 on mouse neutrophils, but not on human neutrophils, activates beta 2-integrin mediated cell attachment to ICAM-1.

Animals↗
PubMed1998

Lymphocyte surface marker and cytokine expression in peripheral and mucosal lymph nodes.

Lymphocyte populations, adhesion molecule and cytokine expression were determined in lymph nodes draining peripheral (popliteal and prescapular) or mucosal (abomasal and jejunal) tissue sites using flow cytometry analysis, immunostaining and cytokine-specific reverse-transcription-polymerase chain reaction (RT-PCR). Similar proportions of lymphocyte subpopulations were present in all lymph nodes except for immunoglobulin A+ (IgA+) B cells which were only present in significant numbers in the gastrointestinal lymph nodes. Peripheral lymph nodes contained a significantly higher number of CD4+ cells expressing L-selectin and beta 1-integrin than mucosal lymph nodes while the alpha 4-integrin chain was expressed at similar levels in all lymph nodes. The peripheral node adressin recognized by the MECA 79 monoclonal antibody (mAb) was mainly expressed on peripheral lymph node vessels. RT-PCR analysis showed that interleukin (IL)-10 and IL-4 were preferentially induced in the gastrointestinal lymph nodes while IL-2 and interferon-gamma (IFN-gamma) were induced in all lymph nodes after polyclonal stimulation. These results indicate that there are substantial differences in the cell populations and microenvironments of lymph nodes draining mucosal and peripheral tissue sites in adult sheep.

Animals↗
PubMed2006

Severe muscular dystrophy in mice that lack dystrophin and alpha7 integrin.

The dystrophin glycoprotein complex links laminin in the extracellular matrix to the cell cytoskeleton. Loss of dystrophin causes Duchenne muscular dystrophy, the most common human X-chromosome-linked genetic disease. The alpha7beta1 integrin is a second transmembrane laminin receptor expressed in skeletal muscle. Mutations in the alpha7 integrin gene cause congenital myopathy in humans and mice. The alpha7beta1 integrin is increased in the skeletal muscle of Duchenne muscular dystrophy patients and mdx mice. This observation has led to the suggestion that dystrophin and alpha7beta1 integrin have complementary functional and structural roles. To test this hypothesis, we generated mice lacking both dystrophin and alpha7 integrin (mdx/alpha7(-/-)). The mdx/alpha7(-/-) mice developed early-onset muscular dystrophy and died at 2-4 weeks of age. Muscle fibers from mdx/alpha7(-/-) mice exhibited extensive loss of membrane integrity, increased centrally located nuclei and inflammatory cell infiltrate, greater necrosis and increased muscle degeneration compared to mdx or alpha7-integrin null animals. In addition, loss of dystrophin and/or alpha7 integrin resulted in altered expression of laminin-alpha2 chain. These results point to complementary roles for dystrophin and alpha7beta1 integrin in maintaining the functional integrity of skeletal muscle.

Animals↗
PubMed1999

Characterization of eosinophil adhesion to TNF-alpha-activated endothelium under flow conditions: alpha 4 integrins mediate initial attachment, and E-selectin mediates rolling.

The multistep model of leukocyte adhesion reveals that selectins mediate rolling interactions and that integrins mediate firm adhesion processes. In this study, the interaction between eosinophils and TNF-alpha-activated HUVEC (second or third passage) was studied under flow conditions (0.8 and 3.2 dynes/cm2). Especially the role of alpha 4 integrins on eosinophils and E-selectin on HUVEC was studied. Inhibition of the integrin alpha 4 chain on eosinophils reduced the number of firmly adhered resting eosinophils to TNF-alpha-stimulated endothelium by 43% whereas the percentage rolling cells increased 2.2-fold compared with untreated control eosinophils. Blocking of E-selectin on the endothelium reduced the number of adherent eosinophils by only 23% and 16%. In this situation, however, hardly any rolling adhesion was observed, and the few rolling cells showed a low rolling velocity. Blocking both alpha 4 integrin on eosinophils and E-selectin on HUVEC reduced the number of adhered eosinophils by 95%. P-selectin did not significantly participate in eosinophil adhesion to TNF-alpha-activated HUVEC. Inhibition of both alpha 4 integrins and beta 2 integrins on eosinophils resulted in a reduction of adhered cells by 65% and a 3-fold increase in percentage rolling cells. Taken together, these results clearly show that resting eosinophils preferentially use constitutively active alpha 4 integrins (alpha 4 beta 1, alpha 4 beta 7) for the first attachment to TNF-alpha-activated HUVEC. In addition, alpha 4 integrins and E-selectin work synergistically in eosinophil adherence to TNF-alpha-activated HUVEC. Although E-selectin is important for eosinophil rolling under these conditions, P-selectin plays only a minor role.

Antigens, CD↗
PubMed2002

Random peptide bacteriophage display as a probe for urokinase receptor ligands.

The urokinase receptor is a multi-functional protein that plays a central role in cell surface plasminogen activation, cell migration, and cell adhesion. We previously demonstrated that high affinity peptide ligands for the urokinase receptor, which are urokinase competitors, can be obtained from a 15mer peptide library (Goodson et al., 1994). In order to probe for additional urokinase receptor binding sites we affinity selected the same bacteriophage library on complexes of soluble urokinase receptor (suPAR) and the receptor binding domain of urokinase, residues 1-48 (uPA1-48). Bacteriophage were isolated which bound to suPAR and suPAR:uPA1-48 complexes with high yield. The peptide sequences encoded by these bacteriophage were distinct from those obtained previously on urokinase receptor expressing cells, and comprise two groups based upon effects on su-PAR:1-anilino-8-napthalene sulfonate (ANS) fluorescence, and vitronectin binding competition. Alanine scanning mutagensis of the soluble peptides was used to define minimal regions and key residues for suPAR binding by competition with the parent bacteriophage. A comparison of these results with sequences of domains of both vitronectin and integrin alpha-chains, which have been reported to be important for urokinase receptor binding, suggests that the homology with the peptide sequences selected is functionally significant.

Alanine↗