Neutrophil short-lived oxidant production: enhancement following onset of sepsis-induced lung injury.
Generation of superoxide anion (O2-) by activated neutrophils (PMN) is implicated in the pathogenesis of endothelial cell injury in sepsis. To quantitate this phenomenon we studied the kinetics of O2- production by PMN following in vivo and in vitro exposure to Pseudomonas aeruginosa. PMN were isolated from young swine before and after a 1-hr infusion with 5 x 10(8) organisms/ml at 0.3 ml/20 kg/min. Baseline PMN were studied in an in vitro system where 1 x 10(6) porcine PMN were incubated with live Pseudomonas for 1 hr at 37 degrees C. Neutrophils from septic pigs exhibited a significantly increased (P less than 0.05) initial rate of O2 production, which was 125% greater at 2 min following initial stimulation than saline controls (P less than 0.001). Neutrophils exposed in vitro displayed a similar enhancement of the rate of O2- production; however, the rate was 3.6 times greater than that noted in vivo. The in vivo change in PMN oxidant generation was associated with a rise in both extravascular lung water (EVLW) and increased bronchoalveolar lavage protein (BAL-P) content. These data suggest that sepsis-induced acute lung injury is accompanied by "priming" of circulating PMN; however, important factors are present in the circulation in sepsis that serve to attenuate the damaging potential of PMN oxidant species.
Carey
P D
PD
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23229.
Jenkins
J K
JK
Byrne
K
K
Schneider
A M
AM
Walsh
C J
CJ
Fowler
A A
AA
Sugerman
H J
HJ
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000737:chemistry; D008168:Lung / Q000473:pathology*; D009504:Neutrophils / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000378:metabolism* / Q000473:pathology; D016897:Respiratory Burst; D012141:Respiratory Tract Infections / Q000378:metabolism* / Q000473:pathology; D013481:Superoxides / Q000378:metabolism*; D013552:Swine
D013481:Superoxides