Role of granulocyte/macrophage colony-stimulating factor in the regulation of murine alveolar macrophage proliferation and differentiation.
Granulocyte/macrophage (GM)-CSF is one of the hemopoietic growth factors that stimulates neutrophilic granulocyte and macrophage production by bone marrow progenitor cells. In this study, the effect of GM-CSF on the growth and differentiation of murine pulmonary alveolar macrophages (PAM) was investigated. In the presence of GM-CSF, normal murine PAM were induced to proliferate and develop into macrophage colonies with a dose-response curve similar to that of bone marrow GM colony-forming cells. PAM also responded to CSF-1, a lineage-restricted growth factor, but required much higher doses of CSF-1 and a longer incubation time for optimal colony formation. The proliferative response of PAM to CSF-1, however, was greatly enhanced by the concurrent addition of low doses of GM-CSF. In contrast, low doses of CSF-1 failed to potentiate the proliferative response of PAM to GM-CSF. Macrophages derived from GM-CSF cultures were rounder and less stretched and possessed less FcR-mediated phagocytic activity than cells produced in CSF-1 cultures. A study with hydrocortisone-induced monocytopenia showed that nearly one half of lung macrophages may be sustained by local proliferation of PAM without the continuous migration of blood monocytes. This study suggests that GM-CSF may play a major role in the production of PAM by two modes of action, 1) direct stimulation of cell proliferation and 2) enhancement of their responsiveness to CSF-1, thereby producing more mature and functionally competent macrophages.
Chen
B D
BD
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201.
Mueller
M
M
Chou
T H
TH
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology / Q000502:physiology*; D004357:Drug Synergism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000502:physiology*; D006854:Hydrocortisone / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis; D011650:Pulmonary Alveoli / Q000166:cytology*; D011961:Receptors, Fc / Q000502:physiology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011961:Receptors, Fc; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006854:Hydrocortisone