title: The role of MIP-1 alpha in the development of systemic inflammatory response and organ injury following trauma hemorrhage.
abstract: Although MIP-1alpha is an important chemokine in the recruitment of inflammatory cells, it remains unknown whether MIP-1alpha plays any role in the development of systemic inflammatory response following trauma-hemorrhage (T-H). C57BL/6J wild type (WT) and MIP-1alpha-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-1alpha 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-1alpha 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-1alpha plays an important role in mediating the acute inflammatory response following T-H. In the absence of MIP-1alpha, acute inflammatory responses were attenuated; rapidly recovered and less remote organ injury was noted following T-H. Thus, interventions that reduce MIP-1alpha levels following T-H should be useful in decreasing the deleterious inflammatory consequence of trauma.
authors.affiliation: Center for Surgical Research and Department of Surgery, University of Alabama, Birmingham, AL 35294, USA.
authors.forename: Chi-Hsun
authors.initials: CH
authors.lastname: Hsieh
authors.forename: Michael
authors.initials: M
authors.lastname: Frink
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Kan
authors.forename: Jun-Te
authors.initials: JT
authors.lastname: Hsu
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D054405:Chemokine CCL3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018925:Chemokines / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000502:physiology*; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009102:Multiple Organ Failure / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009104:Multiple Trauma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D012771:Shock, Hemorrhagic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators