| First Author | Speyer CL | Year | 2004 |
| Journal | Am J Pathol | Volume | 165 |
| Issue | 6 | Pages | 2187-96 |
| PubMed ID | 15579460 | Mgi Jnum | J:94950 |
| Mgi Id | MGI:3522366 | Doi | 10.1016/S0002-9440(10)63268-3 |
| Citation | Speyer CL, et al. (2004) Novel chemokine responsiveness and mobilization of neutrophils during sepsis. Am J Pathol 165(6):2187-96 |
| abstractText | 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. |
