ANTINEUTROPHIL MONOCLONAL-ANTIBODY (1F12) ALTERS SUPEROXIDE ANION RELEASE BY NEUTROPHILS AND KUPFFER CELLS

The formation of oxygen-derived radicals by phagocytes is regulated by chemotactic agents, cytokines, and adhesion molecules, such as CD11b/ CD18 (Mac-1). In the rat system, we investigated the effect of monoclo nal antibody 1F12 against rat neutrophils on hepatic sequestration of neutrophils and superoxide release by hepatic phagocytes. Within 15 mi n after 1F12 injection, there was profound neutropenia, which persiste d for 24 h. The majority of the ''lost'' neutrophils were sequestered in the liver 4 h after treatment. Zymosan-induced superoxide release i n vitro by isolated hepatic neutrophils from 1F12-treated rats was sig nificantly attenuated at 4 and 24 h. The phorbol myristate acetate med iated superoxide release was inhibited 24 h after treatment. Superoxid e anion release by normal adherent neutrophils in the presence of agon ists was also inhibited by 1F12 in vitro. The in vivo administration o f 1F12 primed the Kupffer cells to release superoxide. In vitro treatm ent of Kupffer cells with 1F12 also stimulated superoxide release. Mon oclonal antibody WT.3 (also directed against rat neutrophils), which d oes not cause neutropenia, did not alter superoxide generation by neut rophils and Kupffer cells. These results indicate that 1F12 may be use ful in attenuating inflammation and tissue injury associated with neut rophil activation. However, the activation of Kupffer cells to release toxic oxygen-derived metabolites may predispose the liver to injury i n certain pathological conditions.