Role of granulocyte-macrophage colony-stimulating factor in pulmonary fibrosis induced in mice by bleomycin.
The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in pulmonary fibrosis elicited in mice by the intratracheal instillation of bleomycin was investigated by (1) evaluation of GM-CSF mRNA levels, (2) administration of GM-CSF, and (3) administration of anti-GM-CSF antibody. A significant increase of the GM-CSF mRNA level was evident in the lung RNA on day 5 after bleomycin instillation, but not on day 15. Abdominal infusion of GM-CSF (0.5 micrograms/h during days 7-15) did prevent the collagen deposition induced by bleomycin, as measured by the lung hydroxyproline content on day 15. In contrast, anti-GM-CSF antibody markedly aggravated the collagen deposition. On histological sections the proportion of lungs showing fibrosing alveolitis was decreased by GM-CSF and increased by anti-GM-CSF IgG. The percentage and number of macrophages within the bronchoalveolar lavage (BAL) fluid was increased by GM-CSF infusion and decreased by anti-GM-CSF antibodies. This study demonstrates that pulmonary GM-CSF has an inhibitory influence upon the alveolar remodeling and collagen deposition associated with pulmonary fibrosis.
Piguet
P F
PF
Department of Pathology, University of Geneva, Switzerland.
Grau
G E
GE
de Kossodo
S
S
D000818:Animals; D000911:Antibodies, Monoclonal; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003094:Collagen / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D006909:Hydroxyproline / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011650:Pulmonary Alveoli / Q000503:physiopathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D001761:Bleomycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003094:Collagen; D006909:Hydroxyproline