Journal
JOURNAL OF IMMUNOLOGY
Volume 175, Issue 7, Pages 4653-4661Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.7.4653
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Funding
- NIAID NIH HHS [T32 AI07511, AI-18571, AI-34879] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007337] Funding Source: Medline
- BLRD VA [I01 BX000513] Funding Source: Medline
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Acute inflammatory responses to invading bacteria such as Staphylococcus aureus include mobilization of polymorphonuclear leukocytes (PMN) and extracellular group IIA phospholipase A(2) (gIIA-PLA(2)). Although accumulating coincidentally, the in vitro anti-staphylococcal activities of PMN and gIIA-PLA, have thus far been studied separately. We now show that degradation of S. aureus phospholipids during and after phagocytosis by human PMN requires the presence of extracellular gIIA-PLA(2). The concentration of extracellular gIIA-PLA(2) required to produce bacterial digestion was reduced 10-fold by PMN. The effects of added gIIA-PLA(2), were greater when present before phagocytosis but even apparent when added after S. aureus were ingested by PMN. Related group V and X PLA(2), which are present within PMN granules, do not contribute to bacterial phospholipid degradation during and after phagocytosis even when added at concentrations 30-fold higher than that needed for action of the gIIA-PLA(2). The action of added gIIA-PLA(2) required catalytically active gIIA-PLA(2) and, in PMN, a functional NADPH oxidase but not myeloperoxidase. These findings reveal a novel collaboration between cellular oxygen-dependent and extracellular oxygen independent host defense systems that may be important in the ultimate resolution of S. aureus infections.
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