Effective treatment of the pulmonary fibrosis elicited in mice by bleomycin or silica with anti-CD-11 antibodies.
We treated two types of experimental pulmonary fibrosis elicited in mice by the intratracheal instillation of bleomycin or silica with monoclonal antibodies (mAbs) specific for the leukocytic integrins CD-11a or CD-11b. This treatment completely prevented collagen deposition, as measured by lung hydroxyproline content on Day 15 after instillation. Furthermore, anti CD-11a mAb was also effective when given on Days 20 and 25 and the lung hydroxyproline content determined on Day 30 after instillation, i.e., in the treatment of an established pulmonary fibrosis. Histologic studies indicated that anti CD-11 mAbs attenuated the fibrosing alveolitis induced by silica or bleomycin and in addition markedly decreased the lymphoid infiltration and platelet microthrombi associated with both types of alveolitis. In contrast, these mAbs had little or no effect on the cellularity of the bronchoalveolar lavage, mainly composed of macrophages. In normal mice, anti CD-11 mAbs also decreased the number of interstitial lymphocytes and the lung collagen content. These observations may lead new to therapies for pulmonary fibrosis.
Piguet
P F
PF
Department of Pathology, University of Geneva, Switzerland.
Rosen
H
H
Vesin
C
C
Grau
G E
GE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D001761:Bleomycin; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004353:Drug Evaluation, Preclinical; D016023:Integrins / Q000276:immunology*; D007375:Interleukin-1 / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis; D012822:Silicon Dioxide; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D016023:Integrins; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D012822:Silicon Dioxide