Bradykinin stimulates alveolar macrophages to release neutrophil, monocyte, and eosinophil chemotactic activity.
Bronchial asthma is accompanied with inflammatory cell infiltration in the airway. Because kinin activity was detected in bronchoalveolar lavage fluid (BALF) from asthmatic patients, and because the concentrations of kallikrein and kinins in BALF increased after allergen challenge, we evaluated the potential that bradykinin (BK) might stimulate alveolar macrophages (AM) to release neutrophil, monocyte, and eosinophil chemotactic activity (NCA, MCA, and ECA). To test this hypothesis, bovine AM were isolated by bronchoalveolar lavage and cultured. The supernatant fluids of AM were tested for chemotactic activity by a blind well chamber technique. AM released NCA, MCA, and ECA in response to BK in a dose-and time-dependent manner (p < 0.01). The released activities were chemotactic by checkerboard analysis. Partial characterization and molecular sieve column chromatography revealed that these released activities were heterogeneous, suggesting predominant low-m.w. lipid soluble activity and weak high-m.w. peptide activity. Lipoxygenase inhibitors blocked the release of chemotactic activities (p < 0.01). The chemotactic activities were partly inhibited by leukotriene B4 (LTB4) and platelet-activating factor (PAF) receptor antagonists (p < 0.05, respectively). Immunoreactive LTB4 significantly increased in supernatant fluids in response to BK (p < 0.05), but PAF was detected only two out of six samples stimulated by BK. The receptor responsible for the release of LTB4 involved both BKB1 and BKB2 receptors. These data suggest that BK may stimulate AM and play a role in bronchial inflammation by recruiting inflammatory cells into the airway.
Sato
E
E
First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Koyama
S
S
Nomura
H
H
Kubo
K
K
Sekiguchi
M
M
D000818:Animals; D001249:Asthma / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002417:Cattle; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007975:Leukotriene B4 / Q000032:analysis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008970:Molecular Weight; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000032:analysis; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors
D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D016209:Interleukin-8; D016859:Lipoxygenase Inhibitors; D018945:Monocyte Chemoattractant Proteins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018102:Receptors, Leukotriene B4; C039351:platelet activating factor receptor; D007975:Leukotriene B4; D001920:Bradykinin