Rapid and prominent up-regulation of high-affinity receptor for immunoglobulin G (Fc gamma RI) by cross-linking of beta 2 integrins on polymorphonuclear leukocytes.

Receptors for the Fc region (FcR) of immunoglobulin (Ig)G play essential roles in effector functions of polymorphonuclear leukocytes (PMNs) including the antibody-mediated clearance of microbes. In contrast to the constitutive expression of the low-affinity receptors for IgG (Fc gamma RII [CD32] and Fc gamma RIII [CD16]), the high-affinity receptor Fc gamma RI (CD64) is barely detectable on unactivated PMNs. CD64 expression is induced in a slow kinetic manner by interferon (IFN)-gamma and granulocyte colony-stimulating factor (G-CSF) after 12 to 24 hours of exposure to these agents. We found that the cross-linking of CD11b as well as of CD18 induced comparable rapid increases in CD64 expression on the surface of PMNs, occurring within 15 minutes of exposure. Cross-linking of neither CD11a nor CD11c induced CD64 expression. In contrast to slow induction by IFN-gamma and G-CSF, the integrin-induced rapid CD64 expression did not require RNA synthesis. Genistein, herbimycin A, and 1,2-bis(o-aminophenoxy)ethan-N,N-N',N'-tetraacetic acid blocked the immediate expression of CD64 in a dose-dependent manner, suggesting that the signal is mediated through calcium mobilization and protein tyrosine kinase(s). Such rapid modulation of the high-affinity Fc gamma RI receptor by integrin cross-linking may reflect the requirement for rapid up-regulation of PMN effector functions, after interaction with endothelial cells, platelets or bacteria.