Hypertonicity prevents lipopolysaccharide-stimulated CD11b/CD18 expression in human neutrophils in vitro: role for p38 inhibition.
BACKGROUND
Neutrophil sequestration in the lungs plays an important role in the development of acute respiratory distress syndrome. We previously reported that hypertonic saline resuscitation attenuated lung injury after hemorrhagic shock and lipopolysaccharide (LPS) by abolishing neutrophil CD11b up-regulation. We investigated the mechanism underlying this effect.


METHODS
Human neutrophils were exposed to LPS in the presence or absence of hypertonicity or SB203580 (p38 inhibitor). CD11b and CD14 were studied by immunofluorescence and p38 phosphorylation by immunoblotting.


RESULTS
Hypertonicity had no effect on CD11b or CD14, caused a weak p38 phosphorylation, and completely prevented the LPS-induced p38 phosphorylation and CD11b up-regulation. p38 inhibition also abrogated CD11b up-regulation by LPS.


CONCLUSIONS
MAPKp38 is important in CD11b regulation by LPS. The inhibitory effect of hypertonicity on the LPS-mediated effect may contribute to its protective anti-inflammatory effect observed in vivo. Transient hypertonicity might minimize organ injury in diseases characterized by neutrophil-mediated damage such as ARDS.
Rizoli
S B
SB
Department of Surgery, The Toronto Hospital, and University of Toronto, Ontario, Canada.
Kapus
A
A
Parodo
J
J
Rotstein
O D
OD
D015153:Blotting, Western; D018821:CD18 Antigens / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002470:Cell Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D005455:Fluorescent Antibody Technique; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases; D009504:Neutrophils / Q000378:metabolism*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
D018821:CD18 Antigens; D004791:Enzyme Inhibitors; D006982:Hypertonic Solutions; D007093:Imidazoles; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D011725:Pyridines; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580