The effect of staphylococcal peptidoglycan on polymorphonuclear leukocytes in vitro and in vivo

The ability of Staphylococcus aureus to resist phagocytosis by polymorphonuclear leukocytes (PMN) is thought to be an important virulence factor for this microorganism. We have studied the effect of peptidoglycan (PG) on PMN function in vitro, and on the induction of leukopenia in vivo. Phagocytosis and chemotaxis by human PMN were both inhibited in vitro by prior incubation with as little as 2.5 micrograms PG/ml. Control PMN phagocytized 85% of added bacteria, while PMN treated with PG for 30 minutes phagocytized only 45% of the bacteria. Also, PG-treated PMN did not migrate towards an attractant. Suppression of PMN function by PG could be abolished when PG was incubated with antiserum raised in rabbits against PG. PMN incubated with PG generated a burst in oxygen metabolism as measured by the emission of chemiluminescence. When PG (500 micrograms) was given to rats or guinea pigs, the animal developed an early leukopenia which paralleled a drop in blood pressure and in thrombocyte levels, and in the concentration of hemolytic complement. Leukopenia was less in animals treated with cobravenom; an agent known to deplete complement. Antihistaminics had no effect on the induction of leukopenia by PG. We conclude that PG may be at least partly responsible for leukopenia sometimes observed in patients with life-threatening staphylococcal infections, and this leukopenia might be due to a direct or indirect toxic effect of PG on the PMN.