title: Bradykinin stimulates type II alveolar cells to release neutrophil and monocyte chemotactic activity and inflammatory cytokines.
abstract: In the present study, we evaluated the potential of bradykinin (BK) to induce the release of neutrophil and monocyte chemotactic activity (NCA and MCA) and cytokines from an alveolar type II epithelial cell line, A549 cells. BK stimulated A549 cells to release NCA and MCA in a dose- and time-dependent manner (P < 0.001). Checkerboard analysis revealed that both NCA and MCA involved chemotactic and chemokinetic activity. Molecular sieve column chromatography showed three molecular weight masses (near 19 kd, 8 kd, and 400 d) for NCA and several molecular weight peaks (near 66 kd, 25 kd, 19 kd, 16 kd, and 400 d) for MCA. The release of NCA and MCA was inhibited by cycloheximide and lipoxygenase inhibitors (P < 0.01). The NCA and MCA were inhibited by leukotriene B4 (LTB4) receptor antagonist (P < 0.01), and the concentration of LTB4 was high enough for NCA and MCA. Antibodies to interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) attenuated NCA (P < 0.01), and antibodies to monocyte chemotactic protein-1 (MCP-1), G-CSF, and transforming growth factor (TGF)-beta attenuated MCA (P < 0.01). The levels of IL-8, G-CSF, MCP-1, and TGF-beta increased time dependently (P < 0.01). BK also stimulated the release of ILeukin-6 from A549 cells (P < 0.001). The receptors responsible for the release of NCA, MCA, and individual chemokines involved both BKB1 and BKB2 receptors. These data suggest that BK may stimulate alveolar type II pneumocytes to release inflammatory cytokines, which then may modulate the lung inflammation.
authors.affiliation: The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Koyama
authors.forename: E
authors.initials: E
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Kubo
authors.forename: M
authors.initials: M
authors.lastname: Miura
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: S
authors.initials: S
authors.lastname: Nagai
authors.forename: T
authors.initials: T
authors.lastname: Izumi
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001920:Bradykinin / Q000493:pharmacokinetics / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D002630:Chemotactic Factors / Q000737:chemistry / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000737:chemistry; D003513:Cycloheximide / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D007975:Leukotriene B4 / Q000032:analysis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D010666:Phenylpropionates / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000032:analysis; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D011726:Pyridinium Compounds / Q000494:pharmacology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D044005:Tetrahydroisoquinolines; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D065168:Bradykinin Receptor Antagonists; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D015850:Interleukin-6; D016209:Interleukin-8; D007546:Isoquinolines; D016859:Lipoxygenase Inhibitors; D010666:Phenylpropionates; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018102:Receptors, Leukotriene B4; D044005:Tetrahydroisoquinolines; D016212:Transforming Growth Factor beta; C039351:platelet activating factor receptor; C067523:ONO-LB 457; D016179:Granulocyte Colony-Stimulating Factor; D007975:Leukotriene B4; D003513:Cycloheximide; D001920:Bradykinin; C067430:TCV 309