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Induction of procoagulant activity on human endothelial cells by Streptococcus pneumoniae
S Geelen1, C Bhattacharyya, E Tuomanen
1Laboratory of Molecular Infectious Diseases, Rockefeller University, New York, New York 10021.
Abstract:
The inflammatory response in infection caused by gram-negative organisms involves induction of procoagulant activity (PCA) on human endothelial cells. Although infections caused by gram-positive organisms are also associated with fibrin formation and thrombosis, the bacterial determinants inducing PCA are unknown. This study shows that intact pneumococci and the pneumococcal cell wall efficiently induce PCA on human endothelial cells. Upon exposure of endothelial cells to pneumococci, PCA was first detectable at 30 min, peaked at 2 h, and disappeared by 6 h. The specific activities of encapsulated and unencapsulated strains for induction of PCA were equivalent. Purified pneumococcal cell walls were as potent as endotoxin in induction of PCA. The ability to induce a procoagulant state on endothelial cells is a new biological activity of gram-positive cell walls which promotes the participation of the coagulation cascade in the inflammatory response to disease caused by gram-positive organisms.
Insights
Gram-positive bacteria, specifically pneumococci, trigger procoagulant activity (PCA) in human endothelial cells. This finding reveals a new role for bacterial cell walls in the inflammatory response and thrombosis.
Area of Science:
- Microbiology
- Immunology
- Hematology
Background:
- Gram-negative infections induce procoagulant activity (PCA) in endothelial cells, contributing to inflammation and thrombosis.
- While Gram-positive infections also involve fibrin formation, the specific bacterial factors responsible for inducing PCA remain unidentified.
Purpose of the Study:
- To investigate whether Gram-positive organisms, specifically *Streptococcus pneumoniae* (pneumococci), can induce PCA on human endothelial cells.
- To identify the bacterial components of pneumococci responsible for inducing PCA.
Main Methods:
- Human endothelial cells were exposed to intact pneumococci (encapsulated and unencapsulated strains) and purified pneumococcal cell walls.
- Procoagulant activity (PCA) was measured over time (30 min to 6 h) following exposure.
- The potency of pneumococcal cell walls in inducing PCA was compared to endotoxin.
Main Results:
- Intact pneumococci and purified pneumococcal cell walls efficiently induced PCA on human endothelial cells.
- PCA was detectable within 30 minutes, peaked at 2 hours, and diminished by 6 hours.
- Encapsulated and unencapsulated pneumococcal strains showed equivalent PCA induction. Purified pneumococcal cell walls were as potent as endotoxin in inducing PCA.
Conclusions:
- Gram-positive bacterial cell walls, exemplified by pneumococcal cell walls, possess the novel ability to induce PCA on endothelial cells.
- This procoagulant effect of Gram-positive cell walls contributes to the coagulation cascade's involvement in the inflammatory response to Gram-positive infections.
- The findings identify a new mechanism linking Gram-positive bacterial infections to thrombotic complications.