Bleomycin binding sites on alveolar macrophages.
Previous work has demonstrated that bleomycin can directly stimulate alveolar macrophage secretion of fibroblast growth factors and monocyte chemotactic factors. In this study, rat alveolar macrophages obtained by bronchoalveolar lavage were examined for the presence of bleomycin binding sites, which might mediate this response. The results indicated that alveolar macrophages have specific, saturable, and reversible binding sites. Both high- and low-affinity binding sites were found; each macrophage possessed 6.7 x 10(4) high-affinity sites, with a Kd of 528 nM, and 2.2 x 10(6) low-affinity sites, with a Kd of 65 microM. The Kd of the high-affinity sites corresponds closely to the ED50 obtained from dose-response curves of the bleomycin-stimulated secretion of both fibroblast growth and monocyte chemotactic factors, suggesting that bleomycin stimulation of alveolar macrophage function responses may be mediated by bleomycin interaction with these sites.
Division of Hematology, Albany Medical College, New York 12208.
E M
EM
Denholm
S H
SH
Phan
D000818:Animals; D001665:Binding Sites; D001761:Bleomycin / Q000378:metabolism* / Q000494:pharmacology; D002630:Chemotactic Factors / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D002630:Chemotactic Factors; D006133:Growth Substances; D001761:Bleomycin