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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Gago
L A
LA
Department of Surgery, Denver Health Medical Center, Colorado 80204, USA.
Moore
E E
EE
Partrick
D A
DA
Sauaia
A
A
Davis
C M
CM
Toal
T R
TR
Silliman
C C
CC
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000502:physiology*; D005264:Femoral Fractures / Q000201:enzymology* / Q000276:immunology* / Q000601:surgery; D005594:Fracture Fixation, Intramedullary / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D018375:Neutrophil Activation / Q000502:physiology*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000209:etiology*; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D010741:Phospholipases A; D054467:Phospholipases A2