In vitro and in vivo studies have suggested that human complement component C5a plays a key role in neutrophil injury in the adult respiratory distress syndrome (ARDS). First, using leukocyte aggregometry, we demonstrated that the addition of a recently developed rabbit anti-human polyclonal antibody to C5a des arg to endotoxin-activated plasma prevented leukocyte aggregation in vitro. We then administered the anti-C5a des arg antibody to septic primates (Macaca fascicularis). Three groups of primates, coiltrol, septic, and anti-C5a antibody treated septic, were studied (n = 4 in each group). A 30-min infusion of Escherichia coii (1 X 101/kg) resulted in severe sepsis and ARDS. Primates were killed 4 h after completion of the E. coli infusion. Septic animals not treated with anti-C5a antibody had 75% mortality (3/4), decreased oxygenation, severe pulmonary edema, and profound hypotension. Septic primates treated with antiC5a antibodies did not die and did not develop decreased oxygenation (P < 0.05) or increased extravascular lung water (P < 0.05). They also had a marked recovery in their mean arterial blood pressure (P < 0.05). This study demonstrates that treatment with rabbit anti-human C5a des arg antibodies attenuates ARDS and some of the systemic manifestations of sepsis in nonhuman primates.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.