Hypertonic saline attenuation of polymorphonuclear neutrophil cytotoxicity: timing is everything.
BACKGROUND
The potential to modulate the inflammatory response has renewed interest in hypertonic saline (HTS) resuscitation of injured patients. However, the effect of the timing of HTS treatment with respect to polymorphonuclear neutrophil (PMN) priming and activation remains unexplored. We hypothesized that HTS attenuation of PMN functions requires HTS exposure before priming and activation.


METHODS
Isolated PMN were incubated in HTS (180 mM Na+) before L-alpha-phosphatidylcholine, beta-acetyl-gamma-O-alkyl (PAF)/N-formylmethionyl-leucyl-phenylalanine (fMLP) priming/activation, after priming, or after priming/activation. Superoxide production was measured by the reduction cytochrome c, elastase release by cleavage of AAPV-pNA, and beta2-integrin expression by flow cytometry.


RESULTS
HTS before priming or activation decreased beta2-integrin expression, superoxide production, and elastase release. In contrast, HTS after priming/activation augmented superoxide production and elastase release.


CONCLUSIONS
The timing of HTS is a key variable in the attenuation of PMN cytotoxic functions. Maximal attenuation of cytotoxicity is achieved before priming, whereas HTS exposure after activation augments cytotoxicity.
Ciesla
D J
DJ
Department of Surgery, Denver Health Medical Center, Colorado 80204, USA.
Moore
E E
EE
Zallen
G
G
Biffl
W L
WL
Silliman
C C
CC
D018821:CD18 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D009104:Multiple Trauma / Q000276:immunology; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D010196:Pancreatic Elastase / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D012151:Resuscitation; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology
D018821:CD18 Antigens; D012462:Saline Solution, Hypertonic; D010196:Pancreatic Elastase