Stimulation of rat and murine alveolar macrophage proliferation by lung fibroblasts.
Increases in alveolar macrophage (AM) number occur during chronic inflammation and pulmonary fibrosis. Although the underlying mechanism(s) for such increases remain poorly understood, the overall process is known to involve the local proliferation of the AM. In the present study, we report that AM lavaged from the lungs of rats and mice proliferate in vitro when grown atop lung fibroblasts (LF) or when they are cultured in the presence of LF-conditioned media. Using murine AM and LF, we additionally show that the LF-derived mitogenic cytokines for the AM are macrophage colony-stimulating factor (M-CSF) and granulocyte/macrophage colony-stimulating factor (GM-CSF). Our findings suggest that LF, via the production of M-CSF and GM-CSF, may play an important role in regulating the size of the AM population during chronic inflammatory/fibrogenic lung disorders, and that the complex cytokine network that results in pulmonary fibrogenesis may involve a "coupled reciprocity" between the lung's AM and LF.
Lehnert
B E
BE
Life Sciences Division, Los Alamos National Laboratory, New Mexico 87545.
Valdez
Y E
YE
Lehnert
N M
NM
Park
M S
MS
Englen
M D
MD
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D007377:Interleukin-3 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000166:cytology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008970:Molecular Weight; D011658:Pulmonary Fibrosis / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms
D017077:Culture Media, Conditioned; D007377:Interleukin-3; D015850:Interleukin-6; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor