Role of CC chemokines (macrophage inflammatory protein-1β, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

Nicolas M. Bless, Markus Huber-Lang, Ren Feng Guo, Roscoe L. Warner, Hagen Schmal, Boris J. Czermak, Thomas P. Shanley, Larry D. Crouch, Alex B. Lentsch, Vidya Sarma, Michael S. Mulligan, Hans Peter Friedl, Peter A. Ward

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

The role of the CC chemokines, macrophage inflammatory protein-1β (MIP- 1β), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1β, MCP-1, and RANTES were cloned, the proteins were expressed, and neutralizing Abs were developed. mRNA and protein expression for MIP-1β and MCP-1 were up-regulated during the inflammatory response, while mRNA and protein expression for RANTES were constitutive and unchanged during the inflammatory response. Treatment of rats with anti-MIP-1β Ab significantly decreased vascular permeability by 37% (p = 0.012), reduced neutrophil recruitment into lung by 65% (p = 0.047), and suppressed levels of TNF-α in bronchoalveolar lavage fluids by 61% (p = 0.008). Treatment of rats with anti-rat MCP-1 or anti-rat RANTES had no effect on the development of lung injury. In animals pretreated intratracheally with blocking Abs to MCP-1, RANTES, or MIP-1β, significant reductions in the bronchoalveolar lavage content of these chemokines occurred, suggesting that these Abs had reached their targets. Conversely, exogenously MIP-1β, but not RANTES or MCP-1, caused enhancement of the lung vascular leak. These data indicate that MIP-1β, but not MCP-1 or RANTES, plays an important role in intrapulmonary recruitment of neutrophils and development of lung injury in the model employed. The findings suggest that in chemokine-dependent inflammatory responses in lung CC chemokines do not necessarily demonstrate redundant function.

Original languageEnglish (US)
Pages (from-to)2650-2659
Number of pages10
JournalJournal of Immunology
Volume164
Issue number5
StatePublished - Mar 1 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Bless, N. M., Huber-Lang, M., Guo, R. F., Warner, R. L., Schmal, H., Czermak, B. J., Shanley, T. P., Crouch, L. D., Lentsch, A. B., Sarma, V., Mulligan, M. S., Friedl, H. P., & Ward, P. A. (2000). Role of CC chemokines (macrophage inflammatory protein-1β, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats. Journal of Immunology, 164(5), 2650-2659.