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 monoclonal antibody 1F12 against rat neutrophils on hepatic sequestration of neutrophils and superoxide release by hepatic phagocytes. Within 15 min after 1F12 injection, there was profound neutropenia, which persisted for 24 h. The majority of the "lost" neutrophils were sequestered in the liver 4 h after treatment. Zymosan-induced superoxide release in vitro by isolated hepatic neutrophils from 1F12-treated rats was significantly attenuated at 4 and 24 h. The phorbol myristate acetate mediated superoxide release was inhibited 24 h after treatment. Superoxide anion release by normal adherent neutrophils in the presence of agonists was also inhibited by 1F12 in vitro. The in vivo administration of 1F12 primed the Kupffer cells to release superoxide. In vitro treatment of Kupffer cells with 1F12 also stimulated superoxide release. Monoclonal antibody WT.3 (also directed against rat neutrophils), which does not cause neutropenia, did not alter superoxide generation by neutrophils and Kupffer cells. These results indicate that 1F12 may be useful in attenuating inflammation and tissue injury associated with neutrophil activation. However, the activation of Kupffer cells to release toxic oxygen-derived metabolites may predispose the liver to injury in certain pathological conditions.
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 / Q000494:pharmacology*; D001772:Blood Cell Count; D016923:Cell Death / Q000276:immunology; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005609:Free Radicals / Q000378:metabolism; D007728:Kupffer Cells / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology; D008297:Male; D009503:Neutropenia / Q000473:pathology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D005609:Free Radicals; D013481:Superoxides; D015054:Zymosan; D016650:Fluorescein-5-isothiocyanate; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen