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PubMed1996

Tenascin mediates human glioma cell migration and modulates cell migration on fibronectin.

The role of tenascin in mediating tumor cell migration was studied using two cell migration models. In migration/invasion Transwell assays U251.3 glioma cells rapidly migrated through the 8 mu m pore size membranes onto tenascin- and fibronectin-coated surfaces. In this assay the number of cells migrating onto tenascin was 52.2 +/- 9.6% greater than on fibronectin within 4 hours. To assess cell migration rates and cell morphology, U251.3 migration was examined in a two-dimension spheroid outgrowth assay. The radial distance migrated by U251.3 cells from tumor spheroids was found to be 53.8 +/- 4.9% greater on tenascin than on fibronectin. Cells migrating on tenascin display a very motile appearance, while cells migrating on fibronectin spread and maintain close intercellular contacts. Cell migration in the presence of integrin blocking antibodies demonstrated that migration on tenascin and fibronectin is mediated by distinct integrins, alpha2beta1 and alphavbeta5/alphavbeta3, respectively. Since tenascin is coexpressed in malignant tumor matrices with fibronectin, we assessed the effects of tenascin on U251.3 cell migration mediated by fibronectin. Tenascin was found to provide a positive effect on fibronectin-mediated migration by altering cell morphology and enhancing cell motility. These effects of tenascin on fibronectin-mediated cell migration were inhibited by blocking beta1 and alpha2beta1 integrins. The results suggest that tenascin may play a significant role in promoting tumor cell migration and invasiveness by modulating cell responses to normal matrix components.

Base Sequence↗
PubMed2000

The disintegrin-like domain of the snake venom metalloprotease alternagin inhibits alpha2beta1 integrin-mediated cell adhesion.

The alpha2beta1 integrin is a major collagen receptor that plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Here we describe the isolation of a novel metalloproteinase/disintegrin, which is a potent inhibitor of the collagen binding to alpha2beta1 integrin. This 55-kDa protein (alternagin) and its disintegrin domain (alternagin-C) were isolated from Bothrops alternatus snake venom. Amino acid sequencing of alternagin-C revealed the disintegrin structure. Alternagin and alternagin-C inhibit collagen I-mediated adhesion of K562-alpha2beta1-transfected cells. The IC50 was 134 and 100 nM for alternagin and alternagin-C, respectively. Neither protein interfered with the adhesion of cells expressing alphaIIbeta3, alpha1beta1, alpha5beta1, alpha4beta1 alphavbeta3, and alpha9beta1 integrins to other ligands such as fibrinogen, fibronectin, and collagen IV. Alternagin and alternagin-C also mediated the adhesion of the K562-alpha2beta1-transfected cells. Our results show that the disintegrin-like domain of alternagin is responsible for its ability to inhibit collagen binding to alpha2beta1 integrin.

Amino Acid Sequence↗
PubMed2000

Monoclonal antibodies identify residues 199-216 of the integrin alpha2 vWFA domain as a functionally important region within alpha2beta1.

Integrin alpha2beta1 is the major receptor for collagens in the human body, and the collagen-binding site on the alpha2 subunit von Willebrand factor A-type domain (vWFA domain) is now well defined. However, the biologically important conformational changes that are associated with collagen binding, and the means by which the vWFA domain is integrated into the whole integrin are not completely understood. We have raised monoclonal antibodies against recombinant alpha2 vWFA domain for use as probes of function. Three antibodies, JA202, JA215 and JA218, inhibited binding to collagen, collagen I C-propeptide and E-cadherin, demonstrating that their function is important for structurally diverse alpha2beta1 ligands. Cross-blocking studies grouped the epitopes into two clusters: (I) JA202, the inhibitory antibody, Gi9, and a non-inhibitory antibody, JA208; (II) JA215 and JA218. Both clusters were sensitive to events at the collagen binding site, as binding of Gi9, JA202, JA215 and JA218 were inhibited by collagen peptide, JA208 binding was enhanced by collagen peptide, and binding of JA202 was decreased after mutagenesis of the cation-binding residue Thr(221) to alanine. Binding of cluster I antibodies was inhibited by the anti-functional anti-beta1 antibody Mab13, and binding of Gi9 and JA218 to alpha2beta1 was inhibited by substituting Mn(2+) for Mg(2+), demonstrating that these antibodies were sensitive to changes initiated outside the vWFA domain. Mapping of epitopes showed that JA202 and Gi9 bound between residues 212-216, while JA208 bound between residues 199-216. We have therefore identified two epitope clusters with novel properties; i.e. they are intimately associated with the collagen-binding site, responsive to conformational changes at the collagen-binding site and sensitive to events initiated outside the vWFA domain.

Alanine↗
PubMed2005

Alternagin-C, a disintegrin-like protein from the venom of Bothrops alternatus, modulates alpha2beta1 integrin-mediated cell adhesion, migration and proliferation.

The alpha2beta1 integrin is a major collagen receptor that plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Alternagin-C (ALT-C), a disintegrin-like protein purified from the venom of the Brazilian snake Bothrops alternatus, competitively interacts with the alpha2beta1 integrin, thereby inhibiting collagen binding. When immobilized in plate wells, ALT-C supports the adhesion of fibroblasts as well as of human vein endothelial cells (HUVEC) and does not detach cells previously bound to collagen I. ALT-C is a strong inducer of HUVEC proliferation in vitro. Gene expression analysis was done using an Affimetrix HU-95A probe array with probe sets of approximately 10,000 human genes. In human fibroblasts growing on collagen-coated plates, ALT-C up-regulates the expression of several growth factors including vascular endothelial growth factor, as well as some cell cycle control genes. Up-regulation of the vascular endothelial growth factor gene and other growth factors could explain the positive effect on HUVEC proliferation. ALT-C also strongly activates protein kinase B phosphorylation, a signaling event involved in endothelial cell survival and angiogenesis. In human neutrophils, ALT-C has a potent chemotactic effect modulated by the intracellular signaling cascade characteristic of integrin-activated pathways. Thus, ALT-C acts as a survival factor, promoting adhesion, migration and endothelial cell proliferation after binding to alpha2beta1 integrin on the cell surface. The biological activities of ALT-C may be helpful as a therapeutic strategy in tissue regeneration as well as in the design of new therapeutic agents targeting alpha2beta1 integrin.

Animals↗
PubMed2006

Wound healing in the alpha2beta1 integrin-deficient mouse: altered keratinocyte biology and dysregulated matrix metalloproteinase expression.

The alpha2beta1 integrin, a collagen/laminin receptor, is expressed at high level in the basal cell layer of the epidermis. To define the role of the alpha2beta1 integrin in wound healing, wound repair was extensively evaluated in wild-type and alpha2-null mice in vivo. In addition, the impact of alpha2beta1 integrin-deficiency on the function of primary murine keratinocytes in vitro was analyzed. Our in vivo findings demonstrate that genetic deletion of the alpha2beta1 integrin does not significantly alter the rate of re-epithelialization, collagen deposition, or tensile strength during wound closure in mice. In marked contrast to the observed similarities in wound healing, deletion of the alpha2beta1 integrin resulted in a dramatic increase in neoangiogenesis in the wound microenvironment. In contrast to in vivo studies, primary keratinocytes from alpha2-null mice adhered poorly and displayed impaired migration on type I collagen in vitro. We demonstrate that alpha2beta1 integrin-ligation negatively regulates expression of genes including matrix metalloproteinases both in vivo and in vitro. Furthermore, the changes in gene expression could potentially account for relatively normal wound healing in the alpha2-deficient mouse and our recent observation that suggests an antiangiogenic role for the alpha2beta1 integrin in vivo.

Animals↗
PubMed2006

Alpha2(VIII) collagen substrata enhance endothelial cell retention under acute shear stress flow via an alpha2beta1 integrin-dependent mechanism: an in vitro and in vivo study.

BACKGROUND: Essential to tissue-engineered vascular grafts is the formation of a functional endothelial monolayer capable of resisting the forces of blood flow. This study targeted alpha2(VIII) collagen, a major component of the subendothelial matrix, and examined the ability of and mechanisms by which endothelial cells attach to this collagen under static and dynamic conditions both in vitro and in vivo. METHODS AND RESULTS: Attachment of human endothelial cells to recombinant alpha2(VIII) collagen was assessed in vitro under static and shear conditions of up to 100 dyne/cm2. Alpha2(VIII) collagen supported endothelial cell attachment in a dose-dependent manner, with an 18-fold higher affinity for endothelial cells compared with fibronectin. Cell attachment was significantly inhibited by function-blocking anti-alpha2 (56%) and -beta1 (98%) integrin antibodies but was not RGD dependent. Under flow, endothelial cells were retained at significantly higher levels on alpha2(VIII) collagen (53% and 51%) than either fibronectin (23% and 16%) or glass substrata (7% and 1%) at shear rates of 30 and 60 dyne/cm2, respectively. In vivo studies, using endothelialized polyurethane grafts, demonstrated significantly higher cell retention rates to alpha2(VIII) collagen-coated than to fibronectin-coated prostheses in the midgraft area (P < 0.05) after 24 hours' implantation in the caprine carotid artery. CONCLUSIONS: These studies demonstrate that alpha2(VIII) collagen has the potential to improve both initial cell attachment and retention of endothelial cells on vascular grafts in vivo, which opens new avenues of research into the development of single-stage endothelialized prostheses and the next generation of tissue-engineered vascular grafts.

Animals↗
PubMed2005

Fibrillar type I collagens enhance platelet-dependent thrombin generation via glycoprotein VI with direct support of alpha2beta1 but not alphaIIbbeta3 integrin.

The role of collagens and collagen receptors was investigated in stimulating platelet-dependent thrombin generation. Fibrillar type-I collagens, including collagen from human heart, were most potent in enhancing thrombin generation, in a way dependent on exposure of phosphatidylserine (PS) at the platelet surface. Soluble, non-fibrillar type-I collagen required pre-activation of integrin alpha2beta1 with Mn2+ for enhancement of thrombin generation. With all preparations, blocking of glycoprotein VI (GPVI) with 9O12 antibody abrogated the collagen-enhanced thrombin generation, regardless of the alpha2beta 1 activation state. Blockade of alpha2beta1 alone or antagonism of autocrine thromboxane A2 and ADP were less effective. Blockade of alphaIIbbeta3 with abciximab suppressed thrombin generation in platelet-rich plasma, but this did not abolish the enhancing effect of collagens. The high activity of type-I fibrillar collagens in stimulating GPVI-dependent procoagulant activity was confirmed in whole-blood flow studies, showing that these collagens induced relatively high expression of PS. Together, these results indicate that: i) fibrillar type-I collagen greatly enhances thrombin generation, ii) GPVI-induced platelet activation is principally responsible for the procoagulant activity of fibrillar and non-fibrillar collagens, iii) alpha2beta1 and signaling via autocrine mediators facilitate and amplify this GPVI activity, and iv) alphaIIbbeta3 is not directly involved in the collagen effect.

Anticoagulants↗
PubMed2004

Alpha2beta1 integrin-specific collagen-mimetic surfaces supporting osteoblastic differentiation.

The interactions of osteoblasts with their surrounding extracellular matrix (ECM) are essential for skeletal development, homeostasis, and maintenance of the mature osteoblastic phenotype. Integrins are the principal transducers of ECM signals that regulate this process of osteoblast commitment and differentiation. Several studies indicate that the alpha(2)beta(1) integrin interaction with type I collagen is a crucial signal for the induction of osteoblastic differentiation and matrix mineralization. Integrin alpha(2)beta(1) recognizes the Gly-Phe-Hyp-Gly-Glu-Arg (GFOGER) motif in residues 502-507 of the alpha(1)[I] chain of type I collagen. This study demonstrates that an alpha(2)beta(1) integrin-specific GFOGER peptide triggers the activation of focal adhesion kinase and alkaline phosphatase in MC3T3-E1 murine immature osteoblast-like cells, two events that have been implicated in the osteoblastic differentiation pathway. These GFOGER-peptide surfaces also support the expression of multiple osteoblast-specific genes, including osteocalcin and bone sialoprotein, and induce matrix mineralization in a manner similar to type I collagen. This triple-helical peptide represents a promising surface modification strategy for the design of collagen-mimetic bioadhesive surfaces that support osteoblastic differentiation.

Alkaline Phosphatase↗
PubMed2002

Rhodocetin antagonizes stromal tumor invasion in vitro and other alpha2beta1 integrin-mediated cell functions.

The pleiotropic effects of Calloselasma rhodostoma venom is caused by various toxins, among them kistrin and ancrod, which block platelet activation triggered by RGD-dependent integrins and the blood clotting cascade, respectively. Here, we demonstrate that rhodocetin, another component of this venom, acts as alpha2beta1 integrin inhibiting disintegrin and antagonizes important cellular responses to type I collagen. Cell adhesion, migration, and collagen lattice contraction in vitro were specifically inhibited by rhodocetin, whereas expression of collagen-degrading matrix metalloproteases was differently modulated. Moreover, cell invasion of HT1080 fibrosarcoma cells into a type I collagen matrix, but not into a fibrin gel or a basement membrane-extracted matrigel was efficiently blocked by rhodocetin. Unlike its natural ligand collagen, rhodocetin failed to cluster alpha2beta1 integrin, despite similar binding affinities. Hence, in the absence of focal adhesions cells do not attach firmly to rhodocetin and do not respond with any of alpha2beta1-triggered cell reactions, except for MMP-1 production. Therefore, this disintegrin may be a valuable tool to specifically target stromal tumor invasion and to manipulate other alpha2beta1 integrin-mediated functions, such as excessive scar contraction and fibrosis. Rhodocetin might be therapeutically useful because of its lack of interference with RGD-dependent integrins, low molecular mass, high solubility, and biochemical stability.

Cell Adhesion↗
PubMed2001

Keratinocyte migration requires alpha2beta1 integrin-mediated interaction with the laminin 5 gamma2 chain.

Keratinocyte migration is an absolute requirement for correct epithelialization during the process of wound healing. This process requires changes in extracellular matrix ligand expression as well as changes in ligand-binding affinity of the corresponding cellular integrins. In this study, we attempt to understand the role of laminin 5 in migration by investigating the integrin-mediated interactions of migrating keratinocytes with their newly synthesized laminin 5. We chose to induce migration of freshly isolated NHK in vitro by exposing them to TGF-beta1 which, in addition to promoting epithelial cell migration, is also known to prevent cell proliferation. This important feature allowed the study to be focused on cell migration without interfering with cell proliferation. We confirm that keratinocyte migration on plastic, fibronectin or collagen IV substrates requires endogenous laminin 5 deposition, which is predominantly detected under its unprocessed form. Despite a crucial role for laminin 5 in migration, we show that this process is accompanied by a significant decrease in adhesion to purified laminin 5. Moreover, we provide evidence that the alpha2beta1 integrin interaction with newly synthesized laminin 5 renders the cells more adherent and retards migration. Conversely, we provide evidence that the alpha2beta1 integrin-laminin 5 interaction is absolutely required for keratinocyte migration and that the alpha2beta1 integrin is responsible for cell spreading on laminin 5. Finally, we demonstrate that the alpha2beta1 integrin binding to laminin 5 occurs within the short arm of the gamma2 subunit.

Cell Adhesion↗
PubMed1998

Effects of collagenase-cleavage of type I collagen on alpha2beta1 integrin-mediated cell adhesion.

In this paper we show that collagenase-3 cleavage of type I collagen has a marked effect on alpha2beta1 integrin-mediated interactions with the collagen fragments generated. Isolated alpha2beta1 integrin and alpha2 integrin A-domain were found to bind to both native collagen and native 3/4 fragment and, to a lesser degree, native 1/4 fragment. Whole integrin and integrin A-domain binding were lost after heat denaturation of the collagen fragments. At physiological temperature, cell adhesion to triple-helical 3/4 fragment via alpha2beta1 integrin was still possible; however, no alpha2beta1 integrin-mediated adhesion to the 1/4 fragment was observed. Unwinding of the collagen fragment triple helices by heating to physiological temperatures prior to adsorption to plastic tissue culture plates resulted in total abrogation of HT1080 cell attachment to either fragment. These results provide significant evidence in support of a role for matrix-metalloproteinase cleavage of the extracellular matrix in modifying cell-matrix interactions.

Animals↗
PubMed2000

Polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma: distinct architectural composition revealed by collagen IV, laminin and their integrin ligands (alpha2beta1 and alpha3beta1).

AIMS: Polymorphous low-grade adenocarcinoma (PLGA) and adenoid cystic carcinoma (ACC) are malignant salivary gland tumours bearing many similar histological patterns. This study was undertaken to show how the presence and distribution of collagen IV and laminin, and their ligands (integrin alpha2beta1 and alpha3beta1 components), can reveal histoarchitectural differences which distinguish these two entities. METHODS AND RESULTS: Five cases of ACC and five cases of PLGA from the archives of the Oral Pathology Department of the School of Dentistry of the São Paulo University were submitted to immunostaining with the antibodies to collagen IV, laminin, and integrins alpha2beta1 and alpha3beta1 using the streptavidin-biotin-peroxidase technique. Positive and negative controls were included. PLGA showed a thin line of collagen IV and laminin surrounding structures composed of a single cell layer. Integrins were expressed as a widespread and granular pattern. A thick line of collagen and laminin was observed around the neoplastic structures of ACC. Both integrins were expressed in intercellular spaces and around luminal spaces of tubular structures. CONCLUSIONS: Collagen IV and laminin, and their integrin ligands, are useful in demonstrating that neoplastic ductal units of PLGA are composed of a single cell layer, being distinct from ACC which contains structures composed of two layers of neoplastic cells.

Adenocarcinoma↗
PubMed2004

Structure of the integrin alpha2beta1-binding collagen peptide.

We have determined the 1.8A crystal structure of a triple helical integrin-binding collagen peptide (IBP) with sequence (Gly-Pro-Hyp)(2)-Gly-Phe-Hyp-Gly-Glu-Arg-(Gly-Pro-Hyp)(3). The central GFOGER hexapeptide is recognised specifically by the integrins alpha2beta1, alpha1beta1, alpha10beta1 and alpha11beta1. These integrin/collagen interactions are implicated in a number of key physiological processes including cell adhesion, cell growth and differentiation, and pathological states such as thrombosis and tumour metastasis. Comparison of the IBP structure with the previously determined structure of an identical collagen peptide in complex with the integrin alpha2-I domain (IBP(c)) allows the first detailed examination of collagen in a bound and an unbound state. The IBP structure shows a direct and a water-mediated electrostatic interaction between Glu and Arg side-chains from adjacent strands, but no intra-strand interactions. The interactions between IBP Glu and Arg side-chains are disrupted upon integrin binding. A comparison of IBP and IBP(c) main-chain conformation reveals the flexible nature of the triple helix backbone in the imino-poor GFOGER region. This flexibility could be important to the integrin-collagen interaction and provides a possible explanation for the unique orientation of the three GFOGER strands observed in the integrin-IBP(c) complex crystal structure.

Amino Acid Motifs↗
PubMed2005

Effects of adhesion molecules on the behavior of osteoblast-like cells and normal human fibroblasts on different titanium surfaces.

This study examined the influences of titanium (Ti) discs with similar surface roughnesses (R(a) values), but with different topographies and chemical compositions, on the adhesion, spreading, and the alkaline phosphatase (ALP) activity of osteoblast-like cells and normal human fibroblasts. The presence of adhesion molecules on the Ti surfaces and their effects on cell activity were also investigated. Two types of Ti discs were prepared. One kind was a mechanically polished Ti disc, and the other type was a disc obtained by the heating of hydroxyapatite (HA) dip-coated Ti. Scanning electron microscopy, optical interferometry, and scanning Auger electron spectroscopy were used to examine the surface morphology, roughness, and chemical composition, respectively, of the superficial Ti layer. The two types of Ti discs had different topographies and chemical compositions, but had similar R(a) values. The cells on both surface types had similar behaviors and ALP activities. A biological evaluation of the surface-modified Ti discs showed that the type I collagen coating was functionally active in terms of cell spreading in both types of Ti discs. In the mechanically polished Ti discs, fibronectin was functionally active in the normal human fibroblasts, but not in the osteoblast-like cells. Cell adhesion was slightly better on the heat-treated HA dip-coated Ti discs, but not on the mechanically polished Ti discs. Type I collagen and fibronectin mediated the adhesion and spreading of osteoblast-like cells through alpha2beta1 integrin and alpha5beta1 integrin, respectively. These results suggest that type I collagen might be a good candidate for the biochemical modification of Ti surfaces, particularly those surfaces obtained by heating of HA dip-coated Ti.

Cell Adhesion↗
PubMed2000

Human renal fibroblast contraction of collagen I lattices is an integrin-mediated process.

BACKGROUND: Expression of the beta1 family of integrins allows dermal fibroblasts in wounds to contribute to the healing process through migration, adhesion, synthesis, and rearrangement of extracellular matrix. To date the ability of human renal fibroblasts to reorganize collagens and the role of cell surface receptors in this process remain unknown. METHODS: Renal fibroblasts were grown from the cortical tissue of surgically removed human kidneys. The ability of human renal fibroblasts to reorganize interstitial collagen I was examined in vitro using solidified collagen I lattices. Integrin function was blocked by incubating fibroblasts with isotype-specific antibodies prior to addition to collagen I lattices. RESULTS: Human renal fibroblasts embedded in collagen I lattices progressively decreased lattice diameter to 60.6+/-11.4% of initial diameter at 48 h post-release (P:<0.01). Fibroblasts incubated in the presence of antibody to beta1 integrin failed to contract collagen I lattices, whilst fibroblasts incubated with non-specific antibody reduced lattice diameter to 60.1+/-12.4% of initial diameter at 48 h post-release (P:<0.01). Further characterization of integrin alpha subunits showed that blocking alpha2beta1 integrin prevented lattice contraction (P:<0.05, alpha2beta1 integrin antibody vs non-specific antibody), whilst blocking of alpha5beta1, alpha3beta1 and alpha1beta1 integrins did not influence this process. CONCLUSIONS: We postulate that collagen I fibril rearrangement by human renal fibroblasts in vitro appears to be an integrin-mediated process involving the alpha2beta1 integrin.

Adult↗
PubMed1998

Altered integrin expression and the malignant phenotype: the contribution of multiple integrated integrin receptors.

The integrins are a family of cell surface adhesion receptors that mediate adhesion to either components of the extracellular matrix or to other cells. The beta1 family of integrins represent the major class of cell substrate receptors with specificities primarily for collagens, laminins, and fibronectins. The role of the integrin family of cell surface adhesion receptors in normal mammary gland morphogenesis and the contributions of altered integrin receptor expression to the invasive and metastatic phenotype have been the primary focus of our lab, as well as a number of other laboratories. The alpha2beta1 integrin is expressed at high levels by normal differentiated epithelial cells including those of the normal breast. Using breast cancer as a model, we evaluated changes in integrin expression in malignancy. We and other investigators made the key observation that alpha2beta1 integrin expression is decreased in adenocarcinoma of the breast in a manner that correlates with the stage of differentiation. Studies of other adenocarcinomas have yielded similar results. When the alpha2beta1 integrin was reexpressed in a poorly differentiated mammary carcinoma that expressed no detectable alpha2 integrin subunit, a dramatic reversion of malignant phenotype to a differentiated epithelial phenotype was observed, indicating a critical role for alpha2beta1 expression in mammary gland differentiation. Other laboratories using monoclonal antibodies to competitively inhibit alpha2beta1 integrin adhesion or oncogenic transformation using c-erb2 have confirmed the important role of that alpha2beta1 integrin in mammary gland morphogenesis. Re-expression of the alpha2beta1 integrin also results in upregulation of both the alpha6 and beta4 integrin subunits. To determine the contribution of enhanced alpha6 and beta4 integrin expression to the abrogation of the malignant phenotype by alpha2beta1 integrin expression, we have now separately re-expressed the human alpha6 or beta4 integrin subunit in the breast cancer model.

Breast↗
PubMed2005

Novel collectin/C1q receptor mediates mast cell activation and innate immunity.

Mast cells play a critical role in innate immunity, allergy, and autoimmune diseases. The receptor/ligand interactions that mediate mast cell activation are poorly defined. The alpha2beta1 integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metalloproteinase-1 (MMP-1), endorepellin, and several viruses, has been implicated in normal developmental, inflammatory, and oncogenic processes. We recently reported that alpha2 integrin subunit-deficient mice exhibited markedly diminished neutrophil and IL-6 responses during Listeria monocytogenes- and zymosan-induced peritonitis. Peritoneal mast cells require alpha2beta1 integrin expression for activation in response to pathogens, yet the ligand and molecular mechanisms by which the alpha2beta1 integrin induces activation and cytokine secretion remain unknown. We now report that the alpha2beta1 integrin is a novel receptor for multiple collectins and the C1q complement protein. We demonstrate that the alpha2beta1 integrin provides a costimulatory function required for mast cell activation and cytokine secretion. This finding suggests that the alpha2beta1 integrin is not only important for innate immunity but may serve as a critical target for the regulation of autoimmune/allergic disorders.

Animals↗