Secretory phospholipase A2 cleavage of intravasated bone marrow primes human neutrophils.

Abstract

Recent clinical reports suggest that early femoral intramedullary rod (IMR) fixation in patients with multiple injuries increases the risk of adult respiratory distress syndrome (ARDS). We have shown that lipid-mediated neutrophil (PMN) priming and elevated circulating levels of secretory phospholipase A2 (sPLA2) within the first 24 hours after injury correlate with the development of ARDS. We thus hypothesized that circulating lipid products, generated by sPLA2 cleavage of intravasated bone marrow, prime PMNs for enhanced superoxide anion (O2-) production. Isolated PMNs from healthy volunteers were incubated for 5 minutes with buffer or sPLA2-lysed bone marrow (100 U/mL) collected from trauma patients. After formyl-methionyleucylphenylalanine (fMLP) activation, O2- production was quantified by the superoxide dismutase-inhibitable reduction of cytochrome c. Blood samples were also drawn from five injured patients before and 24 hours after femoral IMR fixation. PMNs were isolated and assessed for in vivo priming. PMNs incubated with sPLA2-lysed bone marrow were primed for more than 3.5 times greater fMLP-induced O2- production. Furthermore, in patients with femoral fractures, PMN O2- release in response to fMLP after IMR fixation was more than 2.5 times higher than before fixation. Collectively, the findings suggest that bone marrow released from acute fracture sites may become a lipid substrate for the elevated sPLA2 levels found in injured patients. The resultant priming of PMNs may thus render the injured patient at risk for ARDS. Although clearly hypothetical at present, we submit that these observations warrant further investigation because of their clinical implications.