The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation
Open accessAbstract
The activation of initiator protein tissue factor (TF) is likely to be a crucial step in the blood coagulation process, which leads to fibrin formation. The stimuli responsible for inducing TF activation are largely undefined. Here we show that the oxidoreductase protein disulfide isomerase (PDI) directly promotes TF-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of mouse carotid arteries, PDI was released at the injury site from adherent platelets and disrupted vessel wall cells. Inhibition of PDI decreased TF-triggered fibrin formation in different in vivo murine models of thrombus formation, as determined by intravital fluorescence microscopy. PDI infusion increased - and, under conditions of decreased platelet adhesion, PDI inhibition reduced - fibrin generation at the injury site, indicating that PDI can directly initiate blood coagulation. In vitro, human platelet-secreted PDI contributed to the activation of cryptic TF on microvesicles (microparticles). Mass spectrometry analyses indicated that part of the extracellular cysteine 209 of TF was constitutively glutathionylated. Mixed disulfide formation contributed to maintaining TF in a state of low functionality. We propose that reduced PDI activates TF by isomerization of a mixed disulfide and a free thiol to an intramolecular disulfide. Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury.
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Cites
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The human protein disulphide isomerase family: substrate interactions and functional properties
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Self-citationFalati, S., Liu, Q., Gross, P., Merrill-Skoloff, G., Chou, J., Vandendries, E., Celi, A., Croce, K., Furie, B. C., & Furie, B. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021868 · Cited by 752
The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor
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Role of the Extrinsic Pathway of Blood Coagulation in Hemostasis and Thrombosis
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Self-citationFalati, S., Gross, P., Merrill-Skoloff, G., Furie, B. C., & Furie, B. (2002) · Nature Medicine · doi:10.1038/nm782 · Cited by 669
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Self-citationMechanisms of Thrombus Formation
Furie, B., & Furie, B. C. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0801082 · Cited by 1,926
Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases
Massberg, S., Grahl, L., von Bruehl, M.-L., Manukyan, D., Pfeiler, S., Goosmann, C., Brinkmann, V., Lorenz, M., Bidzhekov, K., Khandagale, A. B., et al. (2010) · Nature Medicine · doi:10.1038/nm.2184 · Cited by 1,206
Self-citationInterplay between inflammation and thrombosis in cardiovascular pathology
Stark, K., & Massberg, S. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00552-1 · Cited by 1,033
Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19
Bonaventura, A., Vecchié, A., Dagna, L., Martinod, K., Dixon, D. L., Van Tassell, B. W., Dentali, F., Montecucco, F., Massberg, S., Levi, M., et al. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00536-9 · Cited by 987
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Metadata
- Authors
- Reinhardt, C., von Brühl, M.-L., Manukyan, D., Grahl, L., Lorenz, M., Altmann, B., Dlugai, S., Hess, S., Konrad, I., Orschiedt, L., Mackman, N., Ruddock, L., Massberg, S., & Engelmann, B.
- Venue
- Journal of Clinical Investigation
- Published
- 2008-02-01
- Volume
- 118
- Issue
- 3
- Pages
- 1110-22
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2128054798
- Cited by
- 323
- References
- 41
- FWCI
- 16.22
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Reinhardt, C., von Brühl, M.-L., Manukyan, D., Grahl, L., Lorenz, M., Altmann, B., Dlugai, S., Hess, S., Konrad, I., Orschiedt, L., Mackman, N., Ruddock, L., Massberg, S., & Engelmann, B. (2008). Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation. Journal of Clinical Investigation. https://doi.org/10.1172/jci32376
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