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Monocytes and neutrophils contribute to coagulation by expression of tissue factor ( 6, 7), which is upregulated upon inflammation.

Other cells of the circulation and vasculature are altered by inflammatory conditions toward a pro-thrombotic state, as well. Furthermore, chronic inflammation causes a phenotypic switch of vascular smooth muscle cells from a contractile to a synthetic phenotype, which is associated with secretion of pro-inflammatory mediators and which can finally result in a macrophage-like state ( 5). In addition, they undergo a transition toward a more pro-coagulatory phenotype ( 4). However, upon inflammatory stimuli they change their cellular program by expressing leukocytes adhesion molecules to facilitate their entry to sites of inflammation. Endothelial cells in an inactivated, quiescent state express potent inhibitors of coagulation and platelet aggregation. They are also the first immunomodulatory cells at the side of injury and inflammation, providing a functional link between host response and coagulation ( 3). Platelets are the first functional elements that seal damaged blood vessels upon injury by forming aggregates and a subsequent thrombus.

In this review we focus on the cellular interactions that link inflammation with thrombotic processes, while the plasmatic coagulation cascade is described elsewhere ( 1, 2). The close association of inflammatory conditions and coagulatory processes has an evolutionary origin, as injuries require both an efficient blood clotting and an inflammatory immune response against invading pathogens. General Links Between Inflammation and Thrombosis NF-ОєB is critically involved in these pathophysiological processes as it induces both inflammatory and thrombotic responses. Sepsis is an important example of such a disorder caused by a dysregulated host response to infection finally leading to severe coagulopathies. However, deregulation of the complex cellular links between inflammation and thrombosis by unrestrained NET formation or the loss of the endothelial layer due to mechanical rupture or erosion can result in rapid activation and aggregation of platelets and the manifestation of thrombo-inflammatory diseases. This may cause formation of microthrombi that are important for the immobilization of pathogens, a process designated as immunothrombosis.

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Neutrophils respond with an extension of their life span-and upon full activation they can expel their DNA thereby forming so-called neutrophil extracellular traps (NETs), which exert antibacterial functions, but also induce a strong coagulatory response. Monocytes react to inflammatory situations with enforced expression of tissue factor and after differentiation to macrophages with altered polarization.

Paracrine signaling from endothelial cells activates NF-ОєB in vascular smooth muscle cells and causes a phenotypic switch to a вЂњsyntheticвЂќ state associated with a decrease in contractile proteins.

The response of endothelial cells to inflammation and NF-ОєB activation is characterized by the induction of adhesion molecules promoting binding and transmigration of leukocytes, while simultaneously increasing their thrombogenic potential. Even platelets, as anucleated cells, contain NF-ОєB family members and their corresponding signaling molecules, which are involved in platelet activation, as well as secondary feedback circuits. All these cells express NF-ОєB, which mediates important functions in cellular interactions, cell survival and differentiation, as well as expression of cytokines, chemokines, and coagulation factors. In this review, we focus on the role of NF-ОєB signaling in cell types within the vasculature and the circulation that are involved in thrombo-inflammatory processes. The transcription factor NF-ОєB is a central mediator of inflammation with multiple links to thrombotic processes.