Acetylcholine stimulates alveolar macrophages to release inflammatory cell chemotactic activity

Etsuro Sato, Sekiya Koyama, Yoshio Okubo, Keishi Kubo, Morie Sekiguchi
1998 American Journal of Physiology - Lung cellular and Molecular Physiology  
Acetylcholine stimulates alveolar macrophages to release inflammatory cell chemotactic activity. Am. J. Physiol. 274 (Lung Cell. Mol. Physiol. 18): L970-L979, 1998.-Neurological transmitters including ACh, substance P (SP), and calcitonin gene-related peptide (CGRP) play an important role in regulating airway tone, and increased bronchial reactivity to cholinergic stimulation is a well-recognized phenomenon in patients with bronchial asthma. We postulated that ACh, SP, and CGRP might stimulate
more » ... lveolar macrophages (AMs) to release neutrophil, monocyte, and eosinophil chemotactic activities. To test this hypothesis, bovine AMs were isolated by bronchoalveolar lavage and cultured. AMs released chemotactic activities in response to ACh in a dose-and time-dependent manner (P Ͻ 0.05). However, SP and CGRP did not stimulate bovine AMs. Checkerboard analysis revealed that these released activities were predominantly chemotactic. Partial characterization and molecular-sieve column chromatography revealed that low-molecular-weight lipid-soluble activity was predominant. Lipoxygenase inhibitors significantly blocked the release of chemotactic activities (P Ͻ 0.05). Leukotriene B 4 -and plateletactivating factor-receptor antagonists blocked the chemotactic activities. Immunoreactive leukotriene B 4 significantly increased in supernatant fluids in response to ACh (P Ͻ 0.05), but platelet-activating factor did not. The receptor responsible for the release of the chemotactic activities was the muscarinic M 3 receptor. These data demonstrate that ACh stimulates AMs to release lipoxygenase-derived chemotactic activities and plays a role in inflammatory cell recruitment into the airway. leukotriene B 4 ; platelet-activating factor; calcitonin generelated peptide; substance P
doi:10.1152/ajplung.1998.274.6.l970 fatcat:qblb6nr2ajhvdettg4by2634lu