Bombesin down modulates pulmonary fibrosis elicited in mice by bleomycin.
The role of bombesin was investigated in the course of the pulmonary inflammation and fibrosis (PF) elicited by the intratracheal (IT) or intravenous (i.v.) administration of bleomycin in mice. Bleomycin-induced alveolitis was associated with an accumulation of cells, presumably macrophages, containing bombesin, as evidenced by immunohistochemistry. Administration of bombesin by an osmotic minipump implanted IP, at a rate of 6 micrograms/h, decreased the lung hydroxyproline evident 15 days after IV or IT administration of bleomycin. In contrast, antibombesin monoclonal antibody 2A11 (mAb) increased the lung hydroxyproline content after IT administration of bleomycin. In addition, the mortality of bleomycin-injected mice was increased by the anti-bombesin mAb. Bombesin administration induced an increase, and anti-bombesin mAb induced a decrease, in the number of macrophages recovered from the bronchoalveolar lavage. Administration of bombesin did not change the mRNA levels of TNF-alpha, TGF-beta, and PDGF, as seen on Northern blots made with the lung RNA. Pulmonary platelet trapping, which was increased by a bleomycin injection, was decreased by an infusion of bombesin as demonstrated by the distribution of 111In-labeled platelets. This study indicates that bombesin act as an inhibitor of the development of pulmonary fibrosis, possibly by decreasing pulmonary platelet trapping.
Piguet
P F
PF
Department of Pathology, University of Geneva, Switzerland.
Vesin
C
C
Thomas
F
F
D000818:Animals; D000911:Antibodies, Monoclonal; D001761:Bleomycin; D001792:Blood Platelets / Q000187:drug effects; D001839:Bombesin / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D016207:Cytokines / Q000235:genetics; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000401:mortality; D012333:RNA, Messenger / Q000378:metabolism; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D016207:Cytokines; D012333:RNA, Messenger; D001761:Bleomycin; D001839:Bombesin; D006909:Hydroxyproline