Trauma-Hemorrhage Induces Depressed Splenic Dendritic Cell Functions in Mice

Abstract

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-γ production following T-H were significantly decreased. Thus, the markedly decreased MHC class II expression and cytokine (IL-12, IFN-γ) 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.

Trauma and immune response—Effect of gender differences

“…Similar to septic patients, apoptosis was found to be the cause for depletion of dendritic cell in septic mice 21;36;87. Consistent with these studies, findings obtained in our laboratory at two hours after trauma-hemorrhage suggest a suppression in splenic dendritic cell antigen presenting ability and other co-stimulatory functions 44. This was accompanied with decreased MHC class II expression.…”

“…This was accompanied with decreased MHC class II expression. Moreover, LPSinduced IL-12 production following trauma-hemorrhage was significantly decreased 44. While the precise mechanism of suppressed dendritic cell function following trauma-hemorrhage remains to be determined, it is likely that a decreases in MHC class II expression and IL-12 production following trauma-hemorrhage may contribute to suppressed dendritic cell antigen presentation.…”

Establishment of an Experimental Mouse Model of Trauma-Hemorrhagic Shock

“…although there are numerous methods to induce trauma and hemorrhagic shock in mice, there are still many drawbacks associated with these methods. according to the method of Chaudry et al [12], a 20 mm midline laparotomy was performed and then closed in order to induce soft tissue trauma. This method may not be relevant to the clinical setting if, for example, the patient is injured in a road traffic accident.…”

17β-Estradiol's salutary effects on splenic dendritic cell functions following trauma–hemorrhage are mediated via estrogen receptor-α

“…They also have the ability to activate both T helper 1 (Th1) and Th2 cell responses. Our previous studies have shown that trauma-hemorrhage causes a decrease in splenic DCs maturation (Kawasaki et al, 2006). Although treatment with 17β-estradiol following trauma-hemorrhage alters the circulating plasma cytokine levels and improves lymphocyte and macrophage immune functions, it remains unknown whether 17β-estradiol also modulates splenic DC function under those conditions.…”

“…The capacity of purified splenic CD11c-positive cells to present antigen to D10.G4.1 cloned helper T-cells (ATCC, Manassas, VA) was carried out according to the method as previously described (Kawasaki et al, 2006). In brief, the CD11c-positive cells were incubated for 30 min (37°C, 5% CO 2 , in the dark) with 50 μg/ml mitomycin C (Sigma Chemical Co., St. Louis, MO) following which the cells were washed (4 times) in PBS, and a series of dilutions was made.…”