Monocyte chemoattractant protein-1 influences trauma-hemorrhage-induced distal organ damage via regulation of keratinocyte-derived chemokine production

Michael Frink, Ailing Lu, Bjoern M. Thobe, Ya Ching Hsieh, Mashkoor A. Choudhry, Martin G. Schwacha, Steven L. Kunkel, Irshad H. Chaudry

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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.

Original languageEnglish (US)
Pages (from-to)R1110-R1116
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3
StatePublished - Mar 1 2007



  • Cell trafficking
  • Inflammation
  • Neutrophils

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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