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Tissue factor procoagulant expression by rat alveolar epithelial cells.
T J Gross1, R H Simon, R G Sitrin
1Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Summary
Alveolar epithelial cells (AEC) express significant procoagulant activity (PCA), primarily as tissue factor, contributing to intra-alveolar clotting during lung injury. This epithelial-derived PCA, both cell-surface and particulate, plays a key role in modulating lung coagulation.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Hematology
Background:
- Fibrin deposition in alveoli is a hallmark of inflammatory lung injury, stemming from plasma coagulation.
- The specific cells driving intra-alveolar clotting remain incompletely understood.
Purpose of the Study:
- To investigate the procoagulant activity (PCA) of alveolar epithelial cells (AEC).
- To determine if AEC contribute to intra-alveolar coagulation through tissue factor expression.
Main Methods:
- Coagulation assays were performed on rat AEC monolayers and isolated alveolar macrophages.
- Tissue factor identification utilized clotting factor-deficient human plasmas and mRNA hybridization.
- Procoagulant activity on cell surfaces and in shed particles was measured using kinetic assays.
Main Results:
- Rat AEC monolayers exhibited significantly higher PCA (20,750 +/- 4,035 PCU/10(6) cells) than alveolar macrophages.
- Epithelial-derived PCA was identified as tissue factor, confirmed by mRNA expression and functional assays.
- AEC PCA increased with phorbol myristate acetate (PMA) stimulation, paralleling tissue factor mRNA levels.
Conclusions:
- Alveolar epithelial cells possess substantial procoagulant activity, primarily through tissue factor expression.
- AEC contribute to intra-alveolar coagulation via both cell-surface and shed particulate PCA.
- The alveolar epithelium plays a significant role in regulating coagulation within the lung's alveolar space.