The role of MIP-1α in the development of systemic inflammatory response and organ injury following trauma hemorrhage
The role of MIP-1α in the development of systemic inflammatory response and organ injury following trauma hemorrhage
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DOI：
10.4049/jimmunol.181.4.2806
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发表时间：
2008-08-15
影响因子：
4.4
通讯作者：
Chaudry, Irshad H.
中科院分区：
文献类型：
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作者：
Hsieh, Chi-Hsun;Frink, Michael;Chaudry, Irshad H.
虽然MIP-1 α是炎症细胞募集中的重要趋化因子，但MIP-1 α是否在创伤-出血（T-H）后全身炎症反应的发展中发挥任何作用仍不清楚。将C57 BL/6 J野生型（WT）和MIP-1 α缺陷型（KO）小鼠用作对照，进行假手术（插管或仅剖腹手术或插管加剖腹手术）或T-H（中线剖腹手术，平均血压35 +/-5 mmHg持续90分钟，随后复苏），并在2小时后处死。与假手术组或对照组相比，WT T-H小鼠的血清α-谷胱甘肽转移酶、TNF-α、IL-6、IL-10、MCP-1和MIP-1 α以及枯否细胞细胞因子产生显著增加。此外，WT动物T-H后肺和肝组织水肿和中性粒细胞浸润（髓过氧化物酶（MPO）含量）也增加。T-H后，MIP-1 α KO小鼠中这些炎症标志物明显减弱。此外，与2 h相比，T-H后24和48 h，WT和KO小鼠的MPO活性均稳定下降。然而，在KO小鼠中观察到MPO活性在24小时内正常化至假手术水平，但在WT小鼠中未观察到。因此，MIP-1 α在介导T-H后的急性炎症反应中起重要作用。在缺乏MIP-1 α的情况下，急性炎症反应减弱; T-H后迅速恢复，远端器官损伤较少。因此，降低T-H后MIP-1 α水平的干预措施应有助于减少创伤的有害炎症后果。
Although MIP-1 alpha is an important chemokine in the recruitment of inflammatory cells, it remains unknown whether MIP-1 alpha plays any role in the development of systemic inflammatory response following trauma-hemorrhage (T-H). C57BL/6J wild type (WT) and MIP-1 alpha-deficient (KO) mice were used either as control, subjected to sham operation (cannulation or laparotomy only or cannulation plus laparotomy) or T-H (midline laparotomy, mean blood pressure 35 +/- 5 mmHg for 90 min, followed by resuscitation) and sacrificed 2 h thereafter. A marked increase in serum alpha-glutathione transferase, TNF-alpha, IL-6, IL-10, MCP-1, and MIP-1 alpha and Kupffer cell cytokine production was observed in WT T-H mice compared with shams or control. In addition lung and liver tissue edema and neutrophil infiltration (myeloperoxidase (MPO) content) was also increased following T-H in WT animals. These inflammatory markers were markedly attenuated in the MIP-1 alpha KO mice following T-H. Furthermore, compared with 2 h, MPO activities at 24 and 48 h after T-H declined steadily in both WT and KO mice. However, normalization of MPO activities to sham levels within 24 h was seen in KO mice but not in WT mice. Thus, MIP-1 alpha plays an important role in mediating the acute inflammatory response following T-H. In the absence of MIP-1 alpha, acute inflammatory responses were attenuated; rapidly recovered and less remote organ injury was noted following T-H. Thus, interventions that reduce MIP-1 alpha levels following T-H should be useful in decreasing the deleterious inflammatory consequence of trauma.