Antigen-dependent T cell activation drives the formation of signaling microclusters containing the adaptor SLP-76. Costimulatory integrins regulate SLP-76 phosphorylation and could influence SLP-76 microclusters in the integrin-rich periphery of the immune synapse. We report that costimulation by the integrin VLA-4 (alpha4beta1) required SLP-76 domains implicated in microcluster assembly. Pro-a...

Previous studies have shown that 4 1 (very late activation antigen-4 [VLA-4]) and vascular cell adhesion molecule-1 (VCAM-1) play a major role in hematopoietic progenitor cell (HPC) homing to bone marrow (BM). However, the antibody used to block VLA-4 function in the mouse (hybridoma clone PS/2) is not specific to VLA-4 but inhibits both 4 1 and 4 7 integrins. Here we have evaluated the contrib...

CD47 plays an important but incompletely understood role in the innate and adaptive immune responses. CD47, also called integrin-associated protein, has been demonstrated to associate in cis with β1 and β3 integrins. Here we test the hypothesis that CD47 regulates adhesive functions of T-cell α4β1 (VLA-4) and αLβ2 (LFA-1) in in vivo and in vitro models of inflammation. Intravital microscopy stu...

We examined chemotaxis of human plasma cells (PCs) in response to extracellular matrix proteins (ECMs) in the human PC cell lines FR4ds and OPM-1ds. The FR4ds cells expressed beta 1+, beta 3-, alpha 2-, alpha 3-, alpha 4+, alpha 5+, alpha 6+, and alpha v+ integrins, whereas the OPM-1ds cells expressed beta 1+, beta 3-, alpha 2-, alpha 3+, alpha 4+, alpha 5-, alpha 6+, and alpha v+. Fibronectin ...

The leukocyte beta 1 integrin receptor very late activation antigen-4 (VLA-4) (alpha 4 beta 1, CD49d/CD29) binds to vascular cell adhesion molecule-1 (VCAM-1) expressed on cytokine-activated endothelium. A mAb designated 8A2 was identified that stimulated the binding of U937 cells to CHO cells transfected with VCAM-1 cDNA but not endothelial-leukocyte adhesion molecule or CD4 cDNA. mAb 8A2 also...

Atherosclerosis is an inflammatory disease of the vessel wall characterized by monocyte infiltration in response to pro-atherogenic factors such as oxidized lipids. Recently, the role of specific adhesion molecules in this process has been explored. The endothelium overlying atherosclerotic lesions expresses P-selectin and the shoulder regions express vascular cell adhesion molecule-1 (VCAM-1) ...

Acute lymphoblastic leukemia bearing the Philadelphia chromosome is among the most difficult types of ALL to cure. However, the advent of targeted tyrosine kinase inhibitor (TKI) imatinib has ushered in a new era of treatments that have the potential to be less toxic to patients. Integrins and tyrosine kinases play important roles in mediating and transducing signals for cell survival and suppr...

The L1 adhesion molecule is a member of the immunoglobulin superfamily shared by neural and immune cells. In the nervous system L1 can mediate cell binding by a homophilic mechanism. To analyze its function on leukocytes we studied whether L1 could interact with integrins. Here we demonstrate that VLA-5, an RGD-specific fibronectin receptor on a wide variety of cell types, can bind to murine L1...

We have previously shown that engagement of the integrins VLA-4 and VLA-5 to the fibronectin fragment CH-296 in combination with cytokines sustained the capacity of cultured human CD34(+) cells to undergo hematopoiesis in immunodeficient mice for 7 to 12 months, whereas this capacity was rapidly lost in cells cultured in suspension with the same cytokines. In the current study, we assessed the ...