Novel chemokine responsiveness and mobilization of neutrophils during sepsis.

Abstract

Blood neutrophils (PMN) are usually unresponsive to CC chemokines such as monacyte chemotactic protein-1 and macrophage inflammatory protein-1 alpha. In rodents, the lung buildup of PMN as determined by myeloperoxidase (MPO) activity after airway instillation of bacterial lipopolysaccharide (LPS) was independent of MCP-1 and MIP-1 alpha. In striking contrast, during sepsis following cecal ligation and puncture (CLP), blood PMN demonstrated mRNA for CC chemokine receptors. Furthermore, PMN from CLP, but not from sham rodents, bound MCP-1 and MIP-1 alpha and responded chemotactically in vitro to both MCP-1 and MIP-1 alpha. In CCR2(-/-) mice or WT mice treated in vivo with antibodies to either MCP-1 or MIP-1 alpha, MPO activity was greatly attenuated in CLP animals. In CLP mice, increased serum IL-6 levels were found to be dependent on CCR2, MCP-1, and MIP-1 alpha. When PMN from CLP rodents were incubated in vitro with either MCP-1 or MIP-1 alpha, release of IL-6 was also shown. These findings suggest that sepsis fundamentally alters the trafficking of PMN into the lung in a manner that now engages functional responses to CC chemokines.

• Authors: Cecilia L Speyer, Hongwei Gao, Nicholas J Rancilio, Thomas A Neff, Gary B Huffnagle, J Vidya Sarma, Peter A Ward
• Journal: The American journal of pathology (Am J Pathol) Vol. 165 Issue 6 Pg. 2187-96 (Dec 2004) ISSN: 0002-9440 [Print] United States
• PMID: 15579460 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Ccr2 protein, mouse
• Chemokine CCL2
• Chemokine CCL4
• Interleukin-6
• Lipopolysaccharides
• Macrophage Inflammatory Proteins
• RNA, Messenger
• Receptors, CCR2
• Receptors, Chemokine
• Peroxidase

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Cecum (injuries)
• Chemokine CCL2 (antagonists & inhibitors, immunology, metabolism)
• Chemokine CCL4
• Interleukin-6 (metabolism)
• Lipopolysaccharides (pharmacology)
• Lung (cytology, immunology, metabolism)
• Macrophage Inflammatory Proteins (antagonists & inhibitors, immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neutrophils (immunology, metabolism, pathology)
• Peroxidase (metabolism)
• RNA, Messenger (genetics, metabolism)
• Receptors, CCR2
• Receptors, Chemokine (genetics, metabolism, physiology)
• Sepsis (genetics, immunology, metabolism)