Study On The Change And Role Of Interstitial Dendritic Cells In Multiple Organs Dysfunction Syndrome

Objective: To observe the morphological form, quantity and distribution of interstitial dendritic cells in lung, liver and kidney and explore the significance of these dendritic cells and their functional molecules, cytokines and chemokines in immunodissonance, excessive inflammatory and organs injury in multiple organ dysfunction syndrome in order to provide new theory basis for the studies on immunological pathogenic mechanism and clinical treatment of MODS.Methods: The model of MODS was replicated by zymosan injecting into the peritoneal cavity of the C57BL/6 mice, then the mice were randomly divided into groups of normal, 3-6 hours, 12-48 hours, 5-7 days, 10-12 days post trauma. Pathological changes of lung, liver, kidney and interstitial dendritic cells in them were observed by light microscope and transmission electron microscope in each group. Specific surface markers CD205 and CD11c, Costimulatory makers CD80, CD86 and MHC-II molecule, the expression of IL-1β, IL-10 and CGRP in lung, SLC and its receptor CCR7 in lung, CD4+ and CD8+ T lymphocyte subgroup and MHC-II expression by DC/APC in peripheral blood were detected by immunohistochemistry, reverse transcription PCR and flow cytometry methods.Results: Low number interstitial dendritic cells, 5-9‰ of total cells, distributed in lung, liver and kidney of normal mice with a premature form expressing low level of makers CD80, CD86 and MHC-II molecule. In the early stage of injury, interstitial dendritic cells had a proliferation still expressing low level of makers CD80, CD86 and MHC-II molecule. SLC and its receptor CCR7 in lung increased. The level of MHC-II by the mononuclear cells and CD4/8 ratio declined in peripheral blood. In lung the expression of IL-1β, IL-10 and CGRP increased obviously. In the acute injury stage, the pathological and functional changes of organs were more obvious. Interstitial dendritic cells had a continuousproliferation with high expression of CD80, CD86 and MHC-II molecule. SLC and CCR7 in lung both increased. The expression of MHC-II by the mononuclear cells and CD4/8 ratio declined markedly in peripheral blood. In lung the expression of IL-ip increased to the peak. In the remission stage, interstitial dendritic cells still kept on proliferating, but functional molecule decreased to the extent of normal groups. In lung the level of SLC increased continuously, but that of CCR7 began to decline. In MODS stage, the pathological and functional changes of organs were the most severe. Interstitial dendritic cells further proliferated than ever before, and the expression of CD80, CD86 and MHC-II molecule declined to very low level. The expression of MHC-II by the mononuclear cells and CD4/8 ratio declined remarkably in peripheral blood. In lung, the level of SLC increased continuously, but that of CCR7 still kept decreasing and the expression of IL-10 and CGRP reached the peak, but that of IL-ip declined remarkably.Conclusions: 1. the morphological form, quantity and distribution of interstitial dendritic cells of normal mice were described. 2. Changes of the number and activity of interstitial dendritic cells have close relationship with the functional and structural injury of organs in MODS, and they probably influenced and participated in the course of immunological dysfunction of MODS. 3. SLC and its receptor CCR7 were probably an important factor which influences immunological function of interstitial dendritic cells in lung. The level of CCR7 could become one index evaluating the transfer activity of interstitial dendritic cells and immune response ability of body. 4. The number and activity of interstitial dendritic cells in lung correlate with the expression of stimulating-inflammation/anti-inflammation factors in MODS, and interstitial dendritic cells could probably have the ability to influence and regulate the inflammatory factors in organs.