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Procoagulant (thromboplastin) activity in human bronchoalveolar lavage fluids is derived from alveolar macrophages
Abstract:
Fibrin deposition in the alveolar space and the lung interstitium is a prominent feature of many types of inflammatory pulmonary diseases. Cells of the monocyte/macrophage line are the primary cells supplying procoagulant activity in inflammatory lesions. In the present study we found that both lung alveolar macrophages (LAM) and bronchoalveolar lavage fluids (BALF) from humans contained procoagulant activities. The procoagulant in BALF was associated with membrane vesicles which sedimented at 100,000 g for 1 h. By electron microscopy the BALF ultrasediment was seen to consist almost exclusively of membrane material and this was confirmed by monitoring the content of different marker enzymes for specific subcellular structures. Using macrophage membrane markers, at least part of the BALF-ultrasediment was shown to be derived from LAM. On the basis of phospholipase C sensitivity, antibody neutralization and the site of action of the procoagulant in the sequential activation of coagulation factors, both the LAM-associated and the BALF-associated procoagulant activity was identified as thromboplastin (tissue factor) or thromboplastin-factor VII complexes. This suggests that alveolar macrophages and the LAM-derived thromboplastin-containing microvesicles may contribute to intraalveolar and interstitial fibrin deposition in vivo and probably also have consequences for the development of pulmonary fibrosis.
Insights
Lung macrophages release tissue factor on microvesicles, contributing to fibrin deposition and potentially pulmonary fibrosis in inflammatory lung diseases.
Area of Science:
- Pulmonary Medicine
- Hematology
- Cell Biology
Background:
- Fibrin deposition in lung tissues is characteristic of inflammatory pulmonary diseases.
- Monocyte/macrophage cells are key sources of procoagulant activity in inflammation.
Purpose of the Study:
- To investigate the presence and nature of procoagulant activities in human lung alveolar macrophages (LAM) and bronchoalveolar lavage fluid (BALF).
- To determine the cellular origin and biochemical identity of the procoagulant factors.
Main Methods:
- Analysis of procoagulant activity in LAM and BALF.
- Ultracentrifugation of BALF to isolate membrane vesicles.
- Electron microscopy and enzyme marker analysis of BALF sediment.
- Macrophage membrane marker analysis to identify vesicle origin.
- Biochemical characterization including phospholipase C sensitivity and antibody neutralization.
Main Results:
- Both LAM and BALF exhibited significant procoagulant activities.
- The procoagulant in BALF was associated with membrane vesicles derived partly from LAM.
- The procoagulant activity was identified as thromboplastin (tissue factor) or tissue factor-factor VII complexes.
Conclusions:
- Alveolar macrophages and their derived microvesicles containing thromboplastin contribute to fibrin deposition in the lungs.
- This process may play a role in the development of pulmonary fibrosis.