Monocyte chemoattractant protein-1 influences trauma-hemorrhage-induced distal organ damage via regulation of keratinocyte-derived chemokine production.
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.
Frink
Michael
M
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.
Lu
Ailing
A
Thobe
Bjoern M
BM
Hsieh
Ya-Ching
YC
Choudhry
Mashkoor A
MA
Schwacha
Martin G
MG
Kunkel
Steven L
SL
Chaudry
Irshad H
IH
D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood / Q000494:pharmacology*; D018925:Chemokines / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D004487:Edema; D005786:Gene Expression Regulation / Q000187:drug effects; D006470:Hemorrhage / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014947:Wounds and Injuries / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D018932:Chemokine CCL2; D018925:Chemokines