title: Smoke extract stimulates lung epithelial cells to release neutrophil and monocyte chemotactic activity.
abstract: Inflammatory cells accumulate within the lungs of cigarette smokers. Current concepts suggest that these cells can induce protease-antiprotease and/or oxidant-antioxidant imbalance(s), which may damage the normal lung alveolar and interstitial structures. Because type II pneumocytes line the alveolar space, and because the inflammatory cells migrate and reside at the alveolus, we postulated that the type II pneumocytes might release chemotactic activity for neutrophils and monocytes in response to smoke extract. To test this hypothesis, A549 cells were cultured and the supernatant fluids were evaluated for the neutrophil and monocyte chemotactic activity (NCA and MCA) by a blind-well chamber technique. A549 cells released NCA and MCA in response to smoke extract in a dose- and time-dependent manner (P < 0.05). Checkerboard analysis showed that the activity was chemotactic. Partial characterization of NCA and MCA revealed that the activity was partly heat labile, trypsin sensitive, and ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of NCA and MCA. Molecular sieve column chromatography showed multiple peaks for both NCA and MCA. NCA was inhibited by anti-human-interleukin (IL)-8 antibody, granulocyte colony-stimulating factor (G-CSF) antibody, or leukotriene (LT)B4 receptor antagonist. Monocyte chemoattractant protein (MCP)-1 antibody or LTB4 receptor antagonist inhibited MCA. Immunoreactive IL-8, G-CSF, MCP-1, and LTB4 significantly increased in the supernatant fluids in response to smoke extract. These data suggest that the type II pneumocytes may release NCA and MCA and modulate the inflammatory cell recruitment into the lung.
authors.affiliation: The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Masubuchi
authors.forename: S
authors.initials: S
authors.lastname: Koyama
authors.forename: E
authors.initials: E
authors.lastname: Sato
authors.forename: A
authors.initials: A
authors.lastname: Takamizawa
authors.forename: K
authors.initials: K
authors.lastname: Kubo
authors.forename: M
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: S
authors.initials: S
authors.lastname: Nagai
authors.forename: T
authors.initials: T
authors.lastname: Izumi
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D002850:Chromatography, Gel; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000737:chemistry / Q000378:metabolism*; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018945:Monocyte Chemoattractant Proteins / Q000737:chemistry / Q000378:metabolism*; D010947:Plants, Toxic; D010972:Platelet Activating Factor / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D012906:Smoke / Q000009:adverse effects*; D013997:Time Factors; D014026:Nicotiana
chemical_list: D000906:Antibodies; 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; D012906:Smoke; C039351:platelet activating factor receptor; D007975:Leukotriene B4