Bautista A P, Spolarics Z, Jaeschke H, Smith C W, Spitzer J J
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
J Leukoc Biol. 1994 Mar;55(3):328-35. doi: 10.1002/jlb.55.3.328.
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.
吞噬细胞产生氧衍生自由基受趋化因子、细胞因子和黏附分子（如CD11b/CD18，即Mac-1）调控。在大鼠系统中，我们研究了抗大鼠中性粒细胞单克隆抗体1F12对中性粒细胞肝内滞留及肝吞噬细胞超氧化物释放的影响。注射1F12后15分钟内，出现严重的中性粒细胞减少，并持续24小时。治疗4小时后，大多数“丢失”的中性粒细胞滞留于肝脏。来自1F12处理大鼠的分离肝中性粒细胞在体外经酵母聚糖诱导的超氧化物释放在4小时和24小时时显著减弱。治疗24小时后，佛波酯介导的超氧化物释放受到抑制。在体外，1F12也抑制了正常贴壁中性粒细胞在激动剂存在下的超氧阴离子释放。1F12的体内给药使库普弗细胞引发超氧化物释放。用1F12对库普弗细胞进行体外处理也刺激了超氧化物释放。不引起中性粒细胞减少的抗大鼠中性粒细胞单克隆抗体WT.3未改变中性粒细胞和库普弗细胞的超氧化物生成。这些结果表明，1F12可能有助于减轻与中性粒细胞活化相关的炎症和组织损伤。然而，在某些病理条件下，库普弗细胞被激活以释放有毒的氧衍生代谢产物可能使肝脏易受损伤。
