Mobilization of potent plasma bactericidal activity during systemic bacterial challenge -: Role of group IIA phospholipase A2

Extracellular mobilization of Group IIA 14-kD phospholipase A(2) (PLA(2)) in glycogen-induced rabbit inflammatory peritoneal exudates is responsible for the potent bactericidal activity of the inflammatory fluid toward Staphylococcus aureus (1996, J. Clin, Invest. 97:250-257), Because similar levels of PLA(2) are induced in plasma during systemic inflammation, we have tested whether this gives rise to plasma bactericidal activity not present in resting animals. Baboons were injected intravenously (i.v. with a lethal dose of Escherichia coli and plasma or serum was collected before and at hourly intervals after injection. After infusion of bacteria, PLA(2) levels in plasma and serum rose > 100-fold over 24 h to similar to 1 mu g PLA(2)/ml. Serum collected at 24 h possessed potent bactericidal activity toward S. aureus, Streptococcus pyogenes, and encapsulated E. coli not exhibited by serum collected from unchallenged animals. Bactericidal activity toward S. aureus and S. pyogenes was nearly completely blocked by a monoclonal antibody to human Group IIA PLA(2) and addition of purified human Group IIA PLA(2) to prechallenge serum conferred potent antistaphylococcal and antistreptococcal activity equal to that of the 24 h postchallenge serum. PLA(2)-dependent bactericidal activity was enhanced similar to 10x by factor(s) present constitutively in serum or plasma. Bactericidal activity toward encapsulated E. coli was accompanied by extensive bacterial phospholipid degradation mediated, at least in part, by the mobilized Group IIA PLA(2) but depended on the action of other bactericidal factors in the 24-h serum. These findings further demonstrate the contribution of Group IIA PLA(2) to the antibacterial potency of biological fluids and suggest that mobilization of this enzyme during inflammation may play an important role in host defense against invading bacteria.