| Impaired host immunity as well as exaggerated inflammatory response was shown to be crucial for the development of complications following severe trauma. Monocyte/macrophage plays a central role in the innate and acquired immunity. The dysfunction of monocyte/macrophage is of fundamental importance in the development of immune dysfunction after severe injury. In normal, different distributed monocyte/macrophage presents diversities in phenotypes and functions. However, its significance in immune dysfunction after severe trauma hasn't been elucidated clearly up to now. In order to characterize the relationship between the heterogeneity of monocyte/macrophage and the immune dysfunction after severe trauma and try to find some useful clues for target therapy, monocyte/macrophage from peripheral blood (Mo), pulmonary alveolar (AM) and peritoneal cavity (PM) of trauma-hemorrhage in rats were harvested. The abilities of phagocytosis, I-A expression and pro/anti-inflammtory cytokines secretion of different derived monocyte/macrophage were evaluated before and after trauma-hemorrhage continuously and systematically.Results: (1)In normal rats, AM, PM and Mo showed a great functional difference in phagocytosis, expression of I-A, and the secretion of IL-6 and IL-10. (2)After trauma-hemorrhage, the phagocytosis of PM was decreased significantly at the 1st day, but increased gradually at the 4th day, and returned to normal at the 7th day. The depressed phagocytosis of Mo was observed until the 7th day. However, the severer decreasing phagocytosis of AM compared with PM and Mo was found all the phases during our research. (3)The expression of I-A on AM, PM and Mo were suppressed markedly at the 1st day after trauma-hemorrhage. After that, the expression of PM kept lower level during all study period, and that of Mo also decreased until the 7th day. On the contrary, the expression on AM increased over control at the 4th day to the 7th day (4)The secretion of IL-6 by AM increased gradually after trauma-hemorrhage all the 7 days, and that of PM was declined from the 1st to the 4th day, then increased even over the control's at the 7th day. The secretion of IL-6 by Mo was declined gradually all the time and reached the lowest point at the 7th day, the tendency of which was the same as plasma IL-6 level. The secretionof IL-10 by AM and PM were significantly elevated at the 1st day after trauma-hemorrhage and subsequently reached to their peaks at the 4th day, only slight decline was found at the 7th day. However, an ever-increasing secretion of Mo came to see its peak at the 7th day, as well as the changes of the level of IL-10 in the plasma.Conclusions: (1)Monocyte/macrophage from different locations displayed phenotypic and functional heterogeneity in normal rats. (2)The innative phagocytosis of AM, PM and Mo isolated from the injured rats were declined significantly, AM showed more severe influence than others, it suggested that innate immune defense of lung were more sensitive to the trauma-hemorrhage. (3)The expression of I-A on PM was decreased for a long time, which represented the decreased antigen presentation of PM. (4)The high levels of IL-6 and IL-10 were observed on AM early following trauma and lasted during the whole research phase, which might be responsible for the development of ALI and ARDS following trauma. Meanwhile, the increased IL-10 level induced by post-trauma suggested the suppressed immune defense in circulation. Taken together, the phenotypic and functional heterogeneity of monocyte/macrophage from different locations was displayed under normal condition, furthermore, the heterogeneity was more obvious following severe injury, which may play a central role in the immunity dysfunction and the development of complications after trauma. Therefore, the targeted immunomodulatory therapies should be taken into consider for the dysfunction following trauma.
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