Hemin-induced cap formation in lymphocytes: inhibition by protein tyrosine kinase inhibitors

Hemin, an oxidant which is mitogenic for lymphocytes, was found to induce cap formation for Con A sites in murine and human lymphocytes and for IgG and Thy 1.2 sites in murine lymphocytes. Doses of hemin which induced capping also induced a redistribution of actin to a detergent-insoluble form. Similar to hemin, we found that heat shock also induced capping of Con A and IgG sites in murine splenocytes, as well as actin redistribution in human peripheral blood mononuclear cells. Specific inhibitors of protein tyrosine kinases, termed tyrphostins, were found to inhibit hemin-induced cap formation. In addition, ligand-dependent cap formation was also inhibited by tyrphostins. Hemin-induced cap formation may result from alteration in cytoskeletal structure and distribution. In addition, changes in membrane lipid composition induced by phospholipase C-gamma 1, known to be activated by protein tyrosine phosphorylation, may initiate actin polymerization and membrane-site redistribution.