Cell-directed inhibitor of human leukocyte locomotion. Identification of immunoglobulin G as a cell-directed inhibitor in normal human serum.

Abstract

Abstract We purified a CDI of leukocyte locomotion from normal human serum and identified it as IgG. We studied the effect of purified whole IgG, its Fc and Fab fragments, IgA, and IgM on leukocyte locomotion in micropore filters, using measurements of both the distance migrated and the number of cells migrating (mass migration). Based on the distance migrated by the fastest PMNLs, the %I max is 40% ± 13 (mean ± S.D.) for IgG, 46% for the Fc fragment, and 40% for IgA. The inhibitor concentrations producing half-maximal inhibition (K i ) are 0.083 ± 0.053 μM for IgG, 2.4 for the Fc fragment, and 0.042 for IgA. Based on the number of granulocytes migrating into the filters (mass migration response), %I max is 50% ± 10 for IgG, 88% for the Fc fragment, and 72% for IgA. The K i values are 0.051 ± 0.036 μM for IgG, 4.2 for the Fc fragment, and 0.12 for IgA. No effect was observed with the Fab fragment up to a concentration of 33 μM or with IgM up to a concentration of 1.5 μM. The inhibition produced by IgG in the upper compartment of the modified Boyden chamber was not affected by the presence of chemotactic attractant in the lower compartment, indicating that it is an inhibitor of locomotion rather than of the chemotactic response per se and that the observed inhibitory effect of IgG on chemotaxis is actually the result of its effect on locomotion. When IgG was present in the lower compartment with chemotactic factors, neither inhibition nor stimulation was observed. Thus IgG possesses neither chemotactic factor inactivator activity nor chemotactic activity. Consistent with the other previously noted effects of CDI, IgG also inhibits the locomotion of monocytes and decreases the phagocytic responses of both PMNLs and monocytes. Finally, IgG also increases the adherence of neutrophils to nylon fibers. These results indicate that in addition to its other known activities, IgG may be an important regulator of PMNL function. (J Lab Clin Med 98:58, 1981.)