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 ro les in effector functions of polymorphonuclear leukocytes (PMNs) including the antibody-mediated clearance of microbes. In contrast to the constitutiv e expression of the low-affinity receptors for Ige (Fc gamma RII [CD32] and Fc gamma RIII [CD16]), the high-affinity receptor Fc gamma RI (CD64) is ba rely detectable on unactivated PMNs. CD64 expression is induced in a slow k inetic manner by interferon (IFN)-gamma and granulocyte colony-stimulating factor (G-CSF) after 12 to 24 hours of exposure to these agents. We found t hat 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 mi nutes of exposure. Cross-linking of neither CD11a nor CD11c induced CD64 ex pression. In contrast to slow induction by IFN-gamma and G-CSF the integrin -induced rapid CD64 expression did not require RNA synthesis. Genistein, he rbimycin A, and 1,2-bis(o-aminophenoxy)ethan-N,N-N',N' tetraacetic acid blo cked the immediate expression of CD64 in a dose-dependent manner, suggestin g that the signal is mediated through calcium mobilization and protein tyro sine kinase(s). Such rapid modulation of the high-affinity Fc gamma RI rece ptor by integrin cross linking may reflect the requirement for rapid up-reg ulation of PMN effector functions, after interaction with endothelial cells , platelets or bacteria. Int J Hematol. 2000;72:48-54. (C) 2000 The Japanes e Society of Hematology.