ALVEOLAR TYPE II-LIKE CELLS RELEASE G-CSF AS NEUTROPHIL CHEMOTACTIC ACTIVITY

We evaluated the potential of A549 cells, an alveolar type II epitheli al cell line, to release granulocyte colony-stimulating factor (G-CSF) , in addition to interleukin (IL)-8 and leukotriene B-4, as neutrophil chemotactic activity (NCA). Human recombinant IL-1 beta stimulated A5 49 cells to release NCA in a time- and dose-dependent fashion. The rel eased NCA was blocked by mouse anti-human G-CSF polyclonal antibody. M olecular-sieve column chromatography revealed that IL-1 beta induced t he release of a 19- to 20-kDa chemotactic mass that was inhibited by a nti-human G-CSF antibody. IL-1 beta stimulated the release of G-CSF in a dose-dependent fashion, but the time-dependent profile of G-CSF sho wed that the concentration of G-CSF declined after 48 h. Tumor necrosi s factor (TNF)-alpha, Escherichia coli lipopolysaccharide (LPS), and b radykinin (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/mi) as in the supernatant flui d induced neutrophil chemotaxis. G-CSF mRNA was expressed time and dos e dependently at 4 h and declined after 4 h in response to IL-1 beta a s 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 participat e in the regulation of leukocyte extravasation.