Related Experiment Videos
Complement-mediated regulation of tissue factor activity in endothelium
S Saadi1, R A Holzknecht, C P Patte
1Department of Surgery, Duke University, Durham, North Carolina 27710, USA.
The Journal of Experimental Medicine
|December 1, 1995
Summary
Immune responses targeting endothelial cells (EC) can trigger blood clotting by stimulating tissue factor production. This process requires complement activation and interleukin-1 alpha release, highlighting a link between immunity and thrombosis.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Inflammation and immune responses are linked to endothelial cell (EC) injury and thrombus formation.
- The mechanisms by which humoral immunity against the endothelium promotes coagulation are not fully understood.
Purpose of the Study:
- To investigate how anti-endothelial cell (anti-EC) antibodies and complement (C) interaction with EC influences coagulation.
- To elucidate the role of tissue factor (TF) expression and function in this process.
Main Methods:
- Utilized cultured ECs exposed to anti-EC antibodies and complement.
- Assessed tissue factor expression and activity, messenger RNA (mRNA) elaboration, and the role of interleukin-1 alpha (IL-1α).
- Investigated the necessity of complement activation, membrane attack complex (MAC) assembly, and protein synthesis.
Main Results:
- Exposure of ECs to anti-EC antibodies and complement stimulated tissue factor synthesis over 16-42 hours.
- Cell surface TF activity required complement activation and MAC assembly, inhibited by soluble CR1 and absence of C8.
- TF mRNA elaboration occurred over 8-30 hours, requiring protein synthesis and IL-1α release as an intermediate step.
Conclusions:
- Endothelial cell tissue factor production and subsequent coagulation initiation are secondary responses to complement activation.
- Interleukin-1 alpha release is a critical intermediate step, mediating the effect of MAC assembly on ECs to induce TF production.
- These findings reveal a pathway linking immune-mediated EC damage to the initiation of blood coagulation.