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Am. J. Respir. Crit. Care Med., Volume 163, Number 1, January 2001, 226-233

Expression of the Cysteinyl Leukotriene 1 Receptor in Normal Human Lung and Peripheral Blood Leukocytes

DAVID J. FIGUEROA, RICHARD M. BREYER, STEPHANIE K. DEFOE, STACIA KARGMAN, BRUCE L. DAUGHERTY, KRISTINE WALDBURGER, QINGYUN LIU, MICHELLE CLEMENTS, ZHIZEN ZENG, GARY P. O'NEILL, THOMAS R. JONES, KEVIN R. LYNCH, CHRISTOPHER P. AUSTIN, and JILLY F. EVANS

Department of Nephrology, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville, Virginia; Department of Pharmacology, Merck Research Laboratories, West Point, Pennsylvania; Department of Biochemistry and Molecular Biology, Merck Frosst Canada Inc., Dorval, Quebec, Canada; and Department of Immunology, Merck Research Laboratories, Rahway, New Jersey

The cysteinyl leukotrienes (CysLTs) are important mediators of human asthma. Pharmacologic and clinical studies show that the CysLTs exert most of their bronchoconstrictive and proinflammatory effects through activation of a putative, 7-transmembrane domain, G-protein-coupled receptor, the CysLT1 receptor. The initial molecular characterization of the CysLT1 receptor showed by in situ hybridization, the presence of CysLT1 receptor messenger RNA (mRNA) in human lung smooth-muscle cells and lung macrophages. We confirmed the results of these in situ hybridization analyses for the CysLT1 receptor, and produced the first immunohistochemical characterization of the CysLT1 receptor protein in human lung. The identification of the CysLT1 receptor in the lung is consistent with the antibronchoconstrictive and antiinflammatory actions of CysLT1 receptor antagonists. We also report the expression of CysLT1 receptor mRNA and protein in most peripheral blood eosinophils and pregranulocytic CD34+ cells, and in subsets of monocytes and B lymphocytes.




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