MONOCLONAL-ANTIBODY AGAINST THE CD18 ADHESION MOLECULE STIMULATES GLUCOSE-UPTAKE BY THE LIVER AND HEPATIC NONPARENCHYMAL CELLS

Neutrophils and macrophages play an important role in the body's micro bicidal defense and have been implicated in the induction of tissue in jury in reperfusion, endotoxemia and septic shock. Cellular host defen se is accompanied by enhanced glucose use. In this study we examined t he effect of monoclonal antibody 1F12 on in vivo glucose use by select ed tissues and hepatic phagocytes. Monoclonal antibody 1F12 is specifi c for the CD18 adhesion molecule on rat neutrophils and is the only kn own antibody that induces profound neutropenia. The administration of monoclonal antibody 1F12 at a final dose of 2 mg/kg body weight enhanc ed the removal of neutrophils from the circulation within 15 min. Leuk openia was sustained for 24 hr. Large numbers of neutrophils were sequ estered in the liver at 4 hr. Although the number of neutrophils in th e liver at 24 hr after antibody treatment was lower than at 4 hr, thes e values were still higher than those in the saline controls. The rate of glucose metabolism by selected tissues was not significantly alter ed by the antibody, except by the liver, in which use increased 2.7-fo ld vs. the control value at 4 hr after treatment. Hepatocytes, endothe lial cells and Kupffer cells contributed to the increase in the rate o f glucose metabolism by the liver. The rate of glucose metabolism by K upffer cells was significantly elevated at 4 and 24 hr, whereas the ra te of glucose metabolism of hepatocytes and endothelial cells returned to normal at 24 hr. After antibody treatment, the glucose uptake by h epatic sequestered neutrophils was significantly reduced at 4 hr and r eturned to near-normal levels at 24 hr. Another CD18 monoclonal antibo dy (monoclonal antibody WT.3), which does not cause neutropenia, did n ot alter the glucose uptake by tissues and hepatic cells, although it induced slight sequestration of neutrophils in the liver. The N-formyl -met-leu-phe-induced superoxide release by neutrophils was attenuated by monoclonal antibody 1F12 in vitro and in vivo. These data indicate that as a consequence of monoclonal antibody 1F12 treatment, a major p ortion of the neutrophil pool is found in the liver and that Kupffer c ells and endothelial cells become activated. It is postulated that thi s is part of the mechanism for increased clearance of effete leukocyte s from the circulation.