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Updated: Aug 19, 2026
A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization
Published on: January 20, 2023
Pulmonary platelet trapping induced by bleomycin: correlation with fibrosis and involvement of the beta 2 integrins
1Department of Pathology, University of Geneva, Switzerland.
Abstract:
Platelet trapping was explored during the course of bleomycin induced pulmonary fibrosis by the injection of indium-111 labelled platelets and by light and electron microscopy (EM) of the alveolar capillaries. An i.v. injection of bleomycin markedly increased the localization of labelled platelets in the lung (but not in other organs) for about 3 weeks. On day 7 after bleomycin injection, a significant increase in the number of platelets in contact with the alveolar endothelium was seen with EM. Platelet trapping was strongly correlated (P < 0.005) with collagen deposition when examined in mouse strains genetically susceptible (CBA, C57BL/10, BL10 A.2R), or resistant (Balb/c, BL10.D2, BL10.A), to bleomycin induced fibrosis. In addition, several treatments known to decrease bleomycin induced collagen deposition and synthesis, namely administration of antibodies against CD11a, CD11b, TNF-alpha and IL-1ra, also decreased platelet trapping. As evaluated by EM, anti CD11a mAb significantly decreased the number of platelets in contact with the alveolar endothelium. This study indicates that bleomycin induced pulmonary fibrosis is strongly correlated with platelet trapping and that platelets probably interact, via their CD11a, with the CD54 born by the alveolar endothelium.
Insights
Bleomycin-induced pulmonary fibrosis involves significant platelet trapping in the lungs, correlating with collagen deposition. Treatments reducing fibrosis also decrease platelet accumulation, suggesting platelets play a key role via CD11a interactions.
Area of Science:
- Pulmonary Medicine
- Hematology
- Immunology
Background:
- Bleomycin is a chemotherapeutic agent known to induce pulmonary fibrosis.
- The precise mechanisms underlying bleomycin-induced pulmonary fibrosis are not fully understood.
- Platelets are increasingly recognized for their roles beyond hemostasis, including in inflammatory processes.
Purpose of the Study:
- To investigate the role and extent of platelet trapping in bleomycin-induced pulmonary fibrosis.
- To explore the correlation between platelet trapping and collagen deposition.
- To identify potential molecular interactions involved in platelet recruitment during fibrosis.
Main Methods:
- Indium-111 labeled platelets were used to quantify platelet localization in vivo.
- Light and electron microscopy (EM) were employed to examine platelet-endothelial interactions in alveolar capillaries.
- Genetic mouse models with varying susceptibility to bleomycin-induced fibrosis were utilized.
- The effects of blocking antibodies (anti-CD11a, anti-CD11b, anti-TNF-alpha, anti-IL-1ra) on platelet trapping were assessed.
Main Results:
- Bleomycin injection significantly increased labeled platelet localization in the lungs for approximately 3 weeks.
- Electron microscopy revealed an increased number of platelets interacting with alveolar endothelium by day 7 post-bleomycin.
- Platelet trapping strongly correlated with collagen deposition across different mouse strains.
- Treatments known to reduce fibrosis also significantly decreased platelet trapping.
- Anti-CD11a monoclonal antibody (mAb) treatment reduced platelet contact with alveolar endothelium.
Conclusions:
- Platelet trapping is a significant feature of bleomycin-induced pulmonary fibrosis.
- Platelet accumulation is closely linked to collagen deposition in this fibrotic model.
- Platelets likely interact with alveolar endothelium via the CD11a/CD54 pathway, contributing to pulmonary fibrosis development.
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