Neutrophils are primed for cytotoxicity and resist apoptosis in injured patients at risk for multiple organ failure.
BACKGROUND
Postinjury multiple organ failure (MOF) is the result of a dysregulated systemic inflammatory response in which primed neutrophils (PMNs) are sequestered in tissues, vulnerable to activation through secondary insults. Apoptosis is critical to the normal clearance of these sequestered PMNs. Conversely, dysfunctional apoptosis prolongs the PMN functional life span, potentially exacerbating PMN-mediated tissue injury and the development of MOF. We hypothesized that severe trauma, in addition to priming PMNs, provokes dysfunctional PMN apoptosis.


METHODS
Neutrophils were harvested daily from 12 severely injured patients at high risk for MOF, cultured for 24 hours, and assessed for apoptosis with use of acridine orange-ethidium bromide staining and fluorescence microscopy. Priming for elastase release was measured in freshly isolated patient PMNs. Plasma from patients was assessed for its ability to delay apoptosis of normal PMNs.


RESULTS
Four patients (33%) had MOF. Neutrophil apoptosis was profoundly delayed in severely injured patients throughout the 5-day study period. Priming for elastase release was augmented concomitantly. Patients' plasma delayed apoptosis of normal PMNs.


CONCLUSIONS
In patients at high risk for postinjury MOF, PMNs are not only primed for cytotoxicity but also resist apoptosis. The dysfunctional apoptosis is attributed, at least in part, to a plasma-borne mediator. The net effect may facilitate hyperinflammatory organ injury.
Biffl
W L
WL
Department of Surgery, Denver Health Medical Center, CO 80204, USA.
Moore
E E
EE
Zallen
G
G
Johnson
J L
JL
Gabriel
J
J
Offner
P J
PJ
Silliman
C C
CC
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology*; D009504:Neutrophils / Q000473:pathology*; D012306:Risk; D014947:Wounds and Injuries / Q000097:blood*
D019272:Leukocyte Elastase