Alveolar type II-like cells release G-CSF as neutrophil chemotactic activity.
We evaluated the potential of A549 cells, an alveolar type II epithelial cell line, to release granulocyte colony-stimulating factor (G-CSF), in addition to interleukin (IL)-8 and leukotriene B4, as neutrophil chemotactic activity (NCA). Human recombinant IL-1beta stimulated A549 cells to release NCA in a time- and dose-dependent fashion. The released NCA was blocked by mouse anti-human G-CSF polyclonal antibody. Molecular-sieve column chromatography revealed that IL-1beta induced the release of a 19- to 20-kDa chemotactic mass that was inhibited by anti-human G-CSF antibody. IL-1beta stimulated the release of G-CSF in a dose-dependent fashion, but the time-dependent profile of G-CSF showed that the concentration of G-CSF declined after 48 h. Tumor necrosis factor (TNF)-alpha, Escherichia coli lipopolysaccharide (LPS), and bradykinin (BK) stimulated A549 cells to release NCA that was inhibited by anti-G-CSF antibody. The release of G-CSF in response to TNF-alpha, LPS, and BK was significantly increased. The similar concentrations of human recombinant G-CSF (10-1,000 pg/ml) as in the supernatant fluid induced neutrophil chemotaxis. G-CSF mRNA was expressed time and dose dependently at 4 h and declined after 4 h in response to IL-1beta as evaluated by RT-PCR. The expression of G-CSF mRNA was also observed by TNF-alpha, LPS, and BK stimulation. These data suggest that type II alveolar epithelial cells may produce G-CSF as NCA and may participate in the regulation of leukocyte extravasation.
Koyama
S
S
The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390, Japan.
Sato
E
E
Masubuchi
T
T
Takamizawa
A
A
Kubo
K
K
Nagai
S
S
Izumi
T
T
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism / Q000502:physiology; D007700:Kinetics; D007975:Leukotriene B4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010666:Phenylpropionates / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000906:Antibodies; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010666:Phenylpropionates; D014409:Tumor Necrosis Factor-alpha; C067523:ONO-LB 457; D016179:Granulocyte Colony-Stimulating Factor; D007975:Leukotriene B4; D007371:Interferon-gamma; D001920:Bradykinin