Acetylcholine stimulates alveolar macrophages to release inflammatory cell chemotactic activity.
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 alveolar 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 < 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 < 0.05). Leukotriene B4- and platelet-activating factor-receptor antagonists blocked the chemotactic activities. Immunoreactive leukotriene B4 significantly increased in supernatant fluids in response to ACh (P < 0.05), but platelet-activating factor did not. The receptor responsible for the release of the chemotactic activities was the muscarinic M3 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.
Sato
E
E
First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390, Japan.
Koyama
S
S
Okubo
Y
Y
Kubo
K
K
Sekiguchi
M
M
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004804:Eosinophils / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors; D007378:Interleukins / Q000037:antagonists & inhibitors; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D010972:Platelet Activating Factor / Q000096:biosynthesis; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology
D002630:Chemotactic Factors; D018680:Cholinergic Antagonists; D007378:Interleukins; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D007975:Leukotriene B4; D017997:Leukotriene C4; D013373:Substance P; D017998:Leukotriene D4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine