Hypertonic immunomodulation is reversible and accompanied by changes in CD11b expression.
BACKGROUND
In a two-hit model of hemorrhagic shock and lipopolysaccharide (LPS), we previously showed that hypertonic saline (HTS) resuscitation reduced lung sequestration of neutrophils and the accompanying injury. This effect was partially attributed to suppressed expression of the surface adhesion molecule CD11b. This study investigates the duration of this protective effect after a single HTS dose and the usefulness of repeated infusions.


METHODS
The previous two-hit rodent model was used. Neutrophil lung sequestration was measured by bronchoalveolar fluid cell count. CD11b expression was followed by flow cytometry. In vitro studies used isolated human neutrophils.


RESULTS
Eighteen hours following resuscitation, the protective effect of HTS was lost. At this time, LPS caused an increase in both neutrophil lung sequestration and CD11b expression, regardless of the resuscitation regimen used. A second infusion of HTS prevented these changes and restored the lung protection observed earlier. In vitro studies showed that the duration of hypertonic pretreatment is an important determinant of cell responsiveness under the isotonic conditions: Four but not 2 h hypertonic exposure was able to prevent upregulation of CD11b induced by LPS added immediately after reestablishing isotonicity.


CONCLUSIONS
This study demonstrates that HTS resuscitation lessens lung neutrophil sequestration and CD11b surface expression induced by LPS. This protective effect is transient but can be restored by a second HTS infusion suggesting that maintenance of beneficial effect necessitates repeated HTS addition. The reversibility ensures rapid modulation of neutrophil functions, thereby preventing acute tissue damage without causing long-lasting immunosuppression.
D000818:Animals; D015703:Antigens, CD / Q000097:blood / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004926:Escherichia coli; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D016177:Macrophage-1 Antigen / Q000097:blood / Q000235:genetics*; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy*