Regular Article
Hypertonic Immunomodulation Is Reversible and Accompanied by Changes in CD11b Expression

Presented at the Annual Meeting of the Association for Academic Surgery, Seattle,Washington, November 18–22, 1998
https://doi.org/10.1006/jsre.1999.5581Get rights and content

Abstract

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.

Material and 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 vitrostudies 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 vitrostudies 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.

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    Dr. Rizoli is a recipient of a research fellowship from the Heart and Stroke Scientific Research Corporation of Canada. This work was also supported by grants from the Medical Research Council of Canada (A.K. and O.D.R.), the Defense and Civil Institute of Environmental Medicine (O.D.R.), the Crann Memorial Trust, and the Counnaught Fund of the University of Toronto (A.K.).

    2

    To whom correspondence should be addressed at Toronto Hospital–General Division, 200 Elizabeth St. EN9-232, Toronto, ON, Canada M5G 2C4. Fax: 416-595-9486. E-mail:[email protected].

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