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Interface Between Inflammation and Coagulation

  • Chapter
Physiology of Inflammation

Part of the book series: Methods in Physiology Series ((METHPHYS))

Abstract

Blood coagulation maintains the homeostatic balance of internal body fluids against potentially life-threatening blood losses. Acquired or congenitally inherited aberrations of this process result in severe hemorrhagic or thrombotic disorders. Furthermore, dysregulation of coagulation invariably contributes to vascular and atherosclerotic disorders, cancer, infections, and immune-inflammatory diseases. Since coagulation was defined more than 30 years ago as a “waterfall” of sequential, limited proteolytic activation culminating in fibrin formation, our understanding of this process has progressed tremendously. The primary sequences of coagulation proteins have been elucidated at the cDNA and genomic level, the biochemical requirements of substrate recognition and catalysis have been defined, and, in many cases the tertiary structure of coagulation proteins and cofactors has been resolved by X-ray crystallography. What has also emerged is the pivotal role of vascular cells, and of leukocytes in particular, in coagulation. In addition to providing a surface of negatively charged phospholipids to promote assembly of coagulation, recent experimental evidence has also underscored a nonhemostatic function of vascular cells in coagulation. Through the recognition of specialized membrane receptors, the assembly of coagulation proteins on leukocytes and endothelial cells contributes to intracellular signal transduction, modulation of gene expression, synthesis and release of growth factors/cytokines, and regulation of cell-to-cell adhesion. The objective of this chapter is to focus on the ability of coagulation proteins/proteases to act as modulators of leukocyte effector functions, and their far-reaching implications in human diseases. As a unifying theme, coagulation will be proposed as a response to injury, integrating the preservation of the hemostatic balance with host defense and immune-inflammatory responses.

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Altieri, D.C. (2001). Interface Between Inflammation and Coagulation. In: Ley, K. (eds) Physiology of Inflammation. Methods in Physiology Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7512-5_19

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