Attenuation of the pulmonary inflammatory response following butylated hydroxytoluene treatment of cytosolic phospholipase A2 null mice

Amy M. Meyer, Lori D. Dwyer-Nield, Gregory Hurteau, Robert L. Keith, Yanli Ouyang, Brian M. Freed, Lori R. Kisley, Mark W. Geraci, Joseph V. Bonventre, Raphael A. Nemenoff, Alvin M. Malkinson

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12 Scopus citations

Abstract

Administration of butylated hydroxytoluene (BHT) to mice causes lung damage characterized by the death of alveolar type I pneumocytes and the proliferation and subsequent differentiation of type II cells to replace them. Herein, we demonstrate this injury elicits an inflammatory response marked by chemokine secretion, alveolar macrophage recruitment, and elevated expression of enzymes in the eicosanoid pathway. Cytosolic phospholipase A2 (cPLA 2) catalyzes release of arachidonic acid from membrane phospholipids to initiate the synthesis of prostaglandins and other inflammatory mediators. A role for cPLA2 in this response was examined by determining cPLA 2 expression and enzymatic activity in distal respiratory epithelia and macrophages and by assessing the consequences of cPLA2 genetic ablation. BHT-induced lung inflammation, particularly monocyte infiltration, was depressed in cPLA2 null mice. Monocyte chemotactic protein-1 (MCP-1) content in bronchoalveolar lavage fluid increases after BHT treatment but before monocyte influx, suggesting a causative role. Bronchiolar Clara cells isolated from cPLA2 null mice secrete less MCP-1 than Clara cells from wild-type mice, consistent with the hypothesis that cPLA2 is required to secrete sufficient MCP-1 to induce an inflammatory monocytic response.

Original languageEnglish (US)
Pages (from-to)L1260-L1266
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume290
Issue number6
DOIs
StatePublished - Jun 1 2006

Keywords

  • Clara cells
  • Eicosanoids
  • Macrophages

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Meyer, A. M., Dwyer-Nield, L. D., Hurteau, G., Keith, R. L., Ouyang, Y., Freed, B. M., Kisley, L. R., Geraci, M. W., Bonventre, J. V., Nemenoff, R. A., & Malkinson, A. M. (2006). Attenuation of the pulmonary inflammatory response following butylated hydroxytoluene treatment of cytosolic phospholipase A2 null mice. American Journal of Physiology - Lung Cellular and Molecular Physiology, 290(6), L1260-L1266. https://doi.org/10.1152/ajplung.00182.2005