Modulation of integrin function in hematopoietic progenitor cells by CD43 engagement: Possible involvement of protein tyrosine kinase and phospholipase C-gamma

Attachment of cells to extracellular matrix components is critical for the regulation of hematopoiesis. CD43 is a mucin-like transmembrane sialoglycop rotein expressed on the surface of almost all hematopoietic cells. A highly extended structure of extracellular mucin with negative charge may functio n as a repulsive barrier to hematopoietic cells, However, some investigator s have shown that CD43 has proadhesive properties, and engagement of CD43 h as been reported to upregulate integrin-mediated cell adhesion in T cells. We found that cross-linking of CD43 with monoclonal antibodies (MoAbs) enha nced integrin alpha 4 beta 1 (very late antigen [VLA]-4) and alpha 5 beta 1 (VLA-5)-dependent adhesion of human cord blood CD34(+) cells to fibronecti n, CD34(+) CD38(hi), but not CD34(+)CD38(-/low) cells responded significant ly to the stimulus, suggesting that committed, but not stem and more immatu re progenitors are sensitive to CD43-mediated activation of integrin, To el ucidate the molecular mechanism leading to integrin activation, we used the growth factor-dependent cell line MO7e, Cross-linking of CD43 induced tyro sine phosphorylation of several intracellular molecules including the prote in tyrosine kinase Syk, the protooncogene product Cbl, and phospholipase C (PLC)-gamma 2 in MO7e cells. Moreover, protein tyrosine kinase inhibitor he rbimycin A and PLC inhibitor U73122 both blocked CD43-induced enhancement o f adhesion to fibronectin. These results indicate that signals mediated thr ough CD43 may increase integrin affinity to fibronectin via a pathway depen dent on protein tyrosine kinase and PLC-gamma activation in hematopoietic p rogenitors. (C) 1999 by The American Society of Hematology.