ACETYLCHOLINE STIMULATES ALVEOLAR MACROPHAGES TO RELEASE INFLAMMATORYCELL CHEMOTACTIC ACTIVITY

Neurological transmitters including ACh, substance P(SP), and calciton in gene-related peptide (CGRP) play an important role in regulating ai rway tone, and increased bronchial reactivity to cholinergic stimulati on is a well-recognized phenomenon in patients with bronchial asthma. We postulated that ACh, SP, and CGRP might stimulate alveolar macropha ges (AMs) to release neutrophil, monocyte, and eosinophil chemotactic activities. To test this hypothesis, bovine AMs were isolated by bronc hoalveolar lavage and cultured. AMs released chemotactic activities in response to ACh in a dose-and time-dependent manner (P < 0.05). Howev er, SP and CGRP did not stimulate bovine AMs. Checkerboard analysis re vealed that these released activities were predominantly chemotactic. Partial characterization and molecular-sieve column chromatography rev ealed that low-molecular-weight lipid-soluble activity was predominant . Lipoxygenase inhibitors significantly blocked the release of chemota ctic activities (P < 0.05). Leukotriene Bq-and platelet-activating fac tor-receptor antagonists blocked the chemotactic activities. Immunorea ctive leukotriene Bq significantly increased in supernatant fluids in response to ACh (P < 0.05), but platelet-activating factor did not. Th e receptor responsible for the release of the chemotactic activities w as the muscarinic Mg receptor. These data demonstrate that ACh stimula tes AMs to release lipoxygenase-derived chemotactic activities and pla ys a role in inflammatory cell recruitment into the airway.