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Title: Neutrophil apoptosis is delayed by trauma patients' plasma via a mechanism involving proinflammatory phospholipids and protein kinase C. Author: Biffl WL, West KE, Moore EE, Gonzalez RJ, Carnaggio R, Offner PJ, Silliman CC. Journal: Surg Infect (Larchmt); 2001; 2(4):289-93; discussion 294-5. PubMed ID: 12593704. Abstract: BACKGROUND: Delayed apoptosis of primed neutrophils (PMNs) may facilitate PMN-mediated tissue injury leading to multiple organ failure (MOF). We previously reported delayed apoptosis and priming of PMNs in severely injured patients at risk for MOF. Our in vitro and in vivo data have implicated phospholipids in PMN cytotoxicity following trauma and shock. The phospholipid signaling pathway remains to be elucidated, but may involve protein kinase C (PKC). We hypothesized that circulating platelet-activating factor (PAF) and PAF-like proinflammatory phospholipids mediate delayed postinjury PMN apoptosis and that PKC is integral to the signaling pathway. METHODS: Blood was drawn from severely injured patients (n = 6; mean injury severity score = 21 and transfusion = 10 units) at 6 h postinjury. The plasma fraction was isolated and incubated (5% CO(2), 37 degrees C, 24 h) with PMNs harvested from healthy volunteers. Some PMNs were preincubated with a PAF receptor antagonist (WEB 2170, 400 microM) or a PKC inhibitor (Bis I, 1 microM). Apoptotic index (% PMNs undergoing apoptosis) was assessed morphologically. RESULTS: Trauma patients' plasma delayed PMN apoptosis compared with plasma from controls. The PMN apoptotic index was not altered by WEB 2170 or Bis I alone; however, WEB 2170 or Bis I pretreatment abrogated delayed PMN apoptosis in response to trauma patients' plasma. CONCLUSION: Trauma patients' plasma delays apoptosis of PMNs. Our data implicate PAF-like phospholipids in this effect, and PKC appears to be integral in the signaling process. Further elucidation of specific lipids and signaling pathways may reveal clinically accessible therapeutic targets to prevent PMN-mediated hyperinflammation.[Abstract] [Full Text] [Related] [New Search]