PMID- 17095647 OWN - NLM STAT- MEDLINE DCOM- 20070411 LR - 20200930 IS - 0363-6119 (Print) IS - 0363-6119 (Linking) VI - 292 IP - 3 DP - 2007 Mar TI - Monocyte chemoattractant protein-1 influences trauma-hemorrhage-induced distal organ damage via regulation of keratinocyte-derived chemokine production. PG - R1110-6 AB - Leukocyte infiltration, mediated by chemokines, is a key step in the development of organ dysfunction. Lung and liver neutrophil infiltration following trauma-hemorrhage is associated with upregulation of monocyte chemoattractant protein-1 (MCP-1). Because MCP-1 is not a major attractant for neutrophils, we hypothesized that MCP-1 influences neutrophil infiltration via regulation of keratinocyte-derived chemokines (KC). To study this, male C3H/HeN mice were pretreated with MCP-1 antiserum or control serum and subjected to trauma-hemorrhage or sham operation. Animals were killed 4 h after resuscitation. One group of trauma-hemorrhage mice receiving MCP-1 antiserum was also treated with murine KC during resuscitation. Plasma levels and tissue content of MCP-1 and KC were determined by cytometric bead arrays. Immunohistochemistry was performed to determine neutrophil infiltration; organ damage was assessed by edema formation. Treatment with MCP-1 antiserum significantly decreased systemic, lung, and liver levels of MCP-1 and KC following trauma-hemorrhage. This decrease in MCP-1 levels was associated with decreased neutrophil infiltration and edema formation in lung and liver following trauma-hemorrhage. Restitution of KC in mice treated with MCP-1 antiserum restored tissue neutrophil infiltration and edema. These results lead us to conclude that increased levels of MCP-1 cause neutrophil accumulation and distant organ damage by regulating KC production during the postinjury inflammatory response. FAU - Frink, Michael AU - Frink M AD - Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Volker Hall-Suite G094, 1670 University Blvd., Birmingham, AL 35294-0019, USA. FAU - Lu, Ailing AU - Lu A FAU - Thobe, Bjoern M AU - Thobe BM FAU - Hsieh, Ya-Ching AU - Hsieh YC FAU - Choudhry, Mashkoor A AU - Choudhry MA FAU - Schwacha, Martin G AU - Schwacha MG FAU - Kunkel, Steven L AU - Kunkel SL FAU - Chaudry, Irshad H AU - Chaudry IH LA - eng GR - K02 AI 49960/AI/NIAID NIH HHS/United States GR - R01 GM 37127/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20061109 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (Chemokine CCL2) RN - 0 (Chemokines) SB - IM MH - Animals MH - Chemokine CCL2/blood/*pharmacology MH - Chemokines/*biosynthesis/blood/genetics MH - Edema MH - Gene Expression Regulation/drug effects MH - Hemorrhage/*immunology/pathology MH - Immunohistochemistry MH - Keratinocytes/*drug effects/metabolism MH - Liver/drug effects/pathology MH - Lung/drug effects/pathology MH - Male MH - Mice MH - Mice, Inbred C3H MH - Neutrophil Infiltration/drug effects/immunology MH - Time Factors MH - Wounds and Injuries/immunology/*metabolism/pathology EDAT- 2006/11/11 09:00 MHDA- 2007/04/12 09:00 CRDT- 2006/11/11 09:00 PHST- 2006/11/11 09:00 [pubmed] PHST- 2007/04/12 09:00 [medline] PHST- 2006/11/11 09:00 [entrez] AID - 00650.2006 [pii] AID - 10.1152/ajpregu.00650.2006 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2007 Mar;292(3):R1110-6. doi: 10.1152/ajpregu.00650.2006. Epub 2006 Nov 9.