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Trauma-Hemorrhage Induces Depressed Splenic Dendritic Cell Functions in Mice¹

Center for Surgical Research and Department of Surgery, University of Alabama, Birmingham, AL 35294

Although Kupffer cell, splenic, and peritoneal macrophage functions are markedly altered following trauma-hemorrhage (T-H), it remains unclear whether T-H also affects splenic dendritic cell (sDC) functions. We hypothesized that sDC functions will also be compromised following T-H. Male C3H/HeN (6- to 8-wk) mice were randomly assigned to sham operation or T-H. T-H was induced by midline laparotomy and 90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (four times the shed blood volume in the form of Ringer’s lactate). Two hours later, the mice were sacrificed; sDC were isolated; and the changes in their apoptosis, MHC class II expression, and ability to produce costimulatory cytokines and Ag presentation were measured. The results indicate that sDC Ag presentation capacity was significantly decreased and MHC class II expression was also significantly decreased following T-H. Moreover, LPS-induced IL-12 production and LPS- or IL-12-induced IFN- production following T-H were significantly decreased. Thus, the markedly decreased MHC class II expression and cytokine (IL-12, IFN-) production following T-H may be the cause for the depressed sDC Ag presentation under those conditions. This depression in Ag presentation could contribute to the host’s enhanced susceptibility to sepsis following T-H.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant RO1 GM37127.

² Address correspondence and reprint requests to Dr. Irshad H. Chaudry, Center for Surgical Research, University of Alabama, 1670 University Boulevard, Volker Hall, Room G094, Birmingham, AL 35294-0019. E-mail address: Irshad.Chaudry{at}ccc.uab.edu

³ Abbreviations used in this paper: T-H, trauma-hemorrhage; CBA, cytometric bead array; DC, dendritic cell; PI, propidium iodide; sDC, splenic DC.

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