Evidence for LFA-1/ICAM-1 dependent stimulation of protein tyrosine phosphorylation in human B lymphoid cell lines during homotypic adhesion

Abstract

JK32.1 and SKW6.4 are Epstein-Barr virus (EBV)-positive human B cell lines that undergo spontaneous, lymphocyte function-associated antigen 1 (LFA-1) dependent homotypic adhesion in culture. This process is associated with induction of tyrosine phosphoproteins of molecular mass 90, 106, and 120 kDa and could be reproduced when these cells were centrifugationally aggregated. Antibodies to the beta 2 (CD18) chain of LFA-1 interfered with induction of p120, p106, and p90 during cellular aggregation. Response induction was abrogated when cells were incubated with protein tyrosine kinase (PTK) inhibitors (erbstatin, genistein, and geldanomycin) or cytochalasin B prior to aggregation. An in vitro kinase assay did not reveal activation of focal adhesion kinase. Although the role of LFA-1-dependent tyrosine phosphorylation in B cells is uncertain, patients with the leukocyte adhesion defect (LAD) exhibit humoral abnormalities. Moreover, aggregation did not induce specific tyrosine phosphoproteins in an EBV-transformed B cell line from a LAD patient. These results suggest that an LFA-1-dependent PTK pathway may play an important role in human B cell function.

Adhesion through the Interaction of Lymphocyte Function-associated Antigen-1 with Intracellular Adhesion Molecule-1 Induces Tyrosine Phosphorylation of p130 and Its Association with c-CrkII

“…Unlike the ␤ 1 family of integrins, LFA-1-mediated adhesion does not activate or stimulate the phosphorylation of the p125 FAK kinase (Fig. 1) or other members of the c-src gene family (38,48). However, here we demonstrate that adhesion mediated through LFA-1⅐ICAM-1 binding leads to tyrosine phosphorylation of p130 cas .…”

“…Accordingly, it has been reported that phospholipase C␥ is phosphorylated on tyrosine residues upon cross-linking of LFA-1 by antibody (36). It has also been reported that activation of LFA-1 in B cells (JK32.1) and T-cells (JM) results in enhanced tyrosine phosphorylation of a set of yet unknown proteins (37,38). In this report, we demonstrate that activation of LFA-1, by either stimulation of inside out signaling pathways or through a ␤ 2 subunit-specific activating antibody, results in enhanced tyrosine phosphorylation of p130 cas and subsequent association with crkII.…”

Macrophages in vascular inflammation – From atherosclerosis to vasculitis

“…First, cytokines, especially TNF-α, restructure the intercellular junctions, which facilitate leukocyte transmigration (66). Cytokines activate ECs and induce endothelial expression of integrin ligands, especially vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1, which lead to the recruitment of more inflammatory cells into the inflammatory lesions (7, 68, 69). In KD, it has been proposed that inflammatory cells recruited by macrophage cytokines damage the ECs and smooth muscle cells (SMCs), initiating complex inflammatory responses underlying vasculitis (64).…”

Intercellular Adhesion Molecule 1 Promotes HIV-1 Attachment but Not Fusion to Target Cells

“…The intercellular adhesion molecule 1, ICAM-1 (also known as CD54) is expressed by endothelial and immune cells and is involved in several important immunological events, such as activation of CD8 + T cells [29], signaling between lymphoid cells [30], [31], and trans-endothelial migration of leukocytes [32]–[34]. ICAM-1 is a specific ligand for LFA-1 (lymphocyte function-associated antigen-1), which is an integrin-like protein expressed by immune cells [35]–[37].…”