MECHANISM OF INTESTINAL MUCOSAL IMMUNE DYSFUNCTION FOLLOWING TRAUMA-HEMORRHAGE - INCREASED APOPTOSIS ASSOCIATED WITH ELEVATED FAS EXPRESSION IN PEYERS-PATCHES

Although intestinal mucosal immune dysfunction occurs after trauma and hemorrhage and appears to contribute to infectious complications, the mechanism is not known. In this regard, the inappropriate induction o f immune cell apoptosis may contribute to the immune dysfunction follo wing trauma and hemorrhage. To study this, we examined Peyer's patch c ells for evidence of apoptosis and changes in Fas protein expression, as well as alterations in the relative lymphocyte subpopulations after trauma and hemorrhagic shock. Male C3H/HeN mice underwent sham operat ion, trauma (i.e., laparotomy), hemorrhagic shock (mean arterial blood pressure of 35 +/- 5 mmHg for 90 min, followed by adequate crystalloi d resuscitation), or trauma plus hemorrhage. Peyer's patch cells were isolated at 24 and 72 hr after the procedure. The percentage of apopto tic cells, Fas protein expression, and cell percentage of phenotype we re determined by flow cytometry. The results indicate that trauma alon e induced no significant change in the measured parameters, However, ( i) there were a significant decrease in total viable cell yield and an increased apoptosis in Peyer's patch cells at 24 and 72 hr following hemorrhage or trauma plus hemorrhage; (ii) the increased apoptosis in Peyer's patch was predominantly in cells of the E-cell lineage; (iii) the increased apoptosis was associated with an elevated Fas expression . In conclusion, hemorrhage alone or trauma plus hemorrhage can induce increased apoptosis in Peyer's patch cells, which is associated with the increased Fas expression. Thus, apoptotic involution may play an i mportant role in the depression of intestinal mucosal immune function after trauma and hemorrhagic shock. (C) 1997 Academic Press.