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 microbicidal defense and have been implicated in the induction of tissue injury in reperfusion, endotoxemia and septic shock. Cellular host defense is accompanied by enhanced glucose use. In this study we examined the effect of monoclonal antibody 1F12 on in vivo glucose use by selected tissues and hepatic phagocytes. Monoclonal antibody 1F12 is specific for the CD18 adhesion molecule on rat neutrophils and is the only known antibody that induces profound neutropenia. The administration of monoclonal antibody 1F12 at a final dose of 2 mg/kg body weight enhanced the removal of neutrophils from the circulation within 15 min. Leukopenia was sustained for 24 hr. Large numbers of neutrophils were sequestered in the liver at 4 hr. Although the number of neutrophils in the liver at 24 hr after antibody treatment was lower than at 4 hr, these values were still higher than those in the saline controls. The rate of glucose metabolism by selected tissues was not significantly altered by the antibody, except by the liver, in which use increased 2.7-fold vs. the control value at 4 hr after treatment. Hepatocytes, endothelial cells and Kupffer cells contributed to the increase in the rate of glucose metabolism by the liver. The rate of glucose metabolism by Kupffer cells was significantly elevated at 4 and 24 hr, whereas the rate of glucose metabolism of hepatocytes and endothelial cells returned to normal at 24 hr. After antibody treatment, the glucose uptake by hepatic sequestered neutrophils was significantly reduced at 4 hr and returned to near-normal levels at 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
Bautista
A P
AP
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Spolarics
Z
Z
Jaeschke
H
H
Smith
C W
CW
Spitzer
J J
JJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D018821:CD18 Antigens; D004727:Endothelium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001786:Blood Glucose; D018821:CD18 Antigens; D013481:Superoxides; D005947:Glucose