Lipocortin 1 binding to human leukocytes correlates with its ability to inhibit IgG interactions with Fc gamma receptors.

The anti-inflammatory protein lipocortin 1 has been proposed as a mediator of some of the anti-inflammatory actions of glucocorticoid hormones. In view of reported glucocorticoid effects on leukocyte Fc gamma receptors, the effect of short-term lipocortin 1 pre-incubation on expression and IgG binding capacity of human Fc gamma receptors was examined in vitro. The formation of erythrocyte-antibody rosettes, binding of fluoresceinated IgG ligand and the expression of three defined types of Fc gamma receptors were observed following lipocortin 1 treatment. Maximal inhibition of EA rosetting (70%) by peripheral blood mononuclear cells and a 30-50% inhibition of binding of fluoresceinated human IgG1 to purified human monocytes occurred in the presence of 400 nM lipocortin 1 (p < 0.01). However, there was no accompanying decrease in expression of the three known Fc gamma receptor types measured by specific monoclonal antibodies. Similar observations were made for peripheral blood polymorphonuclear cells. On the other hand, IgG binding was not inhibited by lipocortin 1 in lymphocytes or in a panel of cell lines which express Fc gamma receptors and none of these cell types had the capacity to bind lipocortin.