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The role of platelets in the pathogenesis of systemic sclerosis.

Ramirez GA, Franchini S, Rovere-Querini P, Sabbadini MG, Manfredi AA, Maugeri N - Front Immunol (2012)

Bottom Line: Systemic sclerosis (SSc) is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia.Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target.Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including SSc.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milano, Italy.

ABSTRACT
Systemic sclerosis (SSc) is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia. Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target. Platelets show a unique biological behavior, lying at the crossroads between vascular function, innate and adaptive immunity, and regulation of cell proliferation. Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including SSc. In the setting of SSc platelets are detectable in a persistent activated state, which is intimately linked to the concomitant presence of an injured endothelium and to the widespread activation of the innate and adaptive immune system. As a consistent circulating source of bioactive compounds platelets contribute to the development of many characteristic phenomena of SSc, such as fibrosis and impaired vascular tone.

No MeSH data available.


Related in: MedlinePlus

Involvement of platelets in the pathogenesis of SSc. Platelets are stimulated by the injured endothelium and contribute to vascular dysfunction and ischemia by participating in thrombotic events and by releasing vaso-active moieties (such as TXA2). Increased expression of type I collagen as a consequence of tissue fibrosis further enhances platelet activation. On the other hand platelets actively stimulate tissue fibrosis by releasing fibrogenic mediators such as PDGF, TGF-β, lysophospholipids, and serotonin. The interactions of platelets with immune cells in SSc are less clearly understood. Platelets are known sources of active pro-inflammatory mediators like HMGB1, and interestingly increased circulating levels of this prototypic alarmin have been shown to correlate with disease activity in SSc. Moreover evidence is growing about the prominent role of circulating heterotypic aggregates (between platelets and innate immune cells) in the pathogenesis of inflammatory and vascular diseases and recent studies are currently evaluating their impact in the pathogenesis of SSc. Furthermore other studies suggested the existence of a specific network between collagen-reactive T lymphocyte and platelets in SSc. In this latter setting platelet activation would be enhanced by the release of IFNγ and a wider array of cytokines from autoreactive T lymphocyte, which in turn would affect megakaryocyte maturation and platelet basal activation state.
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Figure 1: Involvement of platelets in the pathogenesis of SSc. Platelets are stimulated by the injured endothelium and contribute to vascular dysfunction and ischemia by participating in thrombotic events and by releasing vaso-active moieties (such as TXA2). Increased expression of type I collagen as a consequence of tissue fibrosis further enhances platelet activation. On the other hand platelets actively stimulate tissue fibrosis by releasing fibrogenic mediators such as PDGF, TGF-β, lysophospholipids, and serotonin. The interactions of platelets with immune cells in SSc are less clearly understood. Platelets are known sources of active pro-inflammatory mediators like HMGB1, and interestingly increased circulating levels of this prototypic alarmin have been shown to correlate with disease activity in SSc. Moreover evidence is growing about the prominent role of circulating heterotypic aggregates (between platelets and innate immune cells) in the pathogenesis of inflammatory and vascular diseases and recent studies are currently evaluating their impact in the pathogenesis of SSc. Furthermore other studies suggested the existence of a specific network between collagen-reactive T lymphocyte and platelets in SSc. In this latter setting platelet activation would be enhanced by the release of IFNγ and a wider array of cytokines from autoreactive T lymphocyte, which in turn would affect megakaryocyte maturation and platelet basal activation state.

Mentions: Several studies have revealed an increased responsiveness of SSc platelets to 5-hydroxytryptamine (5HT), adrenaline, ADP, and collagen (Friedhoff et al., 1984; Goodfield et al., 1988; Postlethwaite and Chiang, 2007). More recently SSc platelets were shown to upregulate a specific non-integrin receptor for type I collagen (Chiang et al., 2006). Type I collagen is in turn abundantly expressed in (injured) vessel walls and is one of the main constituent of fibrotic tissues in SSc. Overexpression of the non-integrin receptor for collagen I together with enhanced downstream signaling ultimately leads to further pro-coagulant activation of platelets, which undergo extensive cytoskeletal remodeling and mobilization of intracellular calcium (Postlethwaite and Chiang, 2007; Figure 1).


The role of platelets in the pathogenesis of systemic sclerosis.

Ramirez GA, Franchini S, Rovere-Querini P, Sabbadini MG, Manfredi AA, Maugeri N - Front Immunol (2012)

Involvement of platelets in the pathogenesis of SSc. Platelets are stimulated by the injured endothelium and contribute to vascular dysfunction and ischemia by participating in thrombotic events and by releasing vaso-active moieties (such as TXA2). Increased expression of type I collagen as a consequence of tissue fibrosis further enhances platelet activation. On the other hand platelets actively stimulate tissue fibrosis by releasing fibrogenic mediators such as PDGF, TGF-β, lysophospholipids, and serotonin. The interactions of platelets with immune cells in SSc are less clearly understood. Platelets are known sources of active pro-inflammatory mediators like HMGB1, and interestingly increased circulating levels of this prototypic alarmin have been shown to correlate with disease activity in SSc. Moreover evidence is growing about the prominent role of circulating heterotypic aggregates (between platelets and innate immune cells) in the pathogenesis of inflammatory and vascular diseases and recent studies are currently evaluating their impact in the pathogenesis of SSc. Furthermore other studies suggested the existence of a specific network between collagen-reactive T lymphocyte and platelets in SSc. In this latter setting platelet activation would be enhanced by the release of IFNγ and a wider array of cytokines from autoreactive T lymphocyte, which in turn would affect megakaryocyte maturation and platelet basal activation state.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3376452&req=5

Figure 1: Involvement of platelets in the pathogenesis of SSc. Platelets are stimulated by the injured endothelium and contribute to vascular dysfunction and ischemia by participating in thrombotic events and by releasing vaso-active moieties (such as TXA2). Increased expression of type I collagen as a consequence of tissue fibrosis further enhances platelet activation. On the other hand platelets actively stimulate tissue fibrosis by releasing fibrogenic mediators such as PDGF, TGF-β, lysophospholipids, and serotonin. The interactions of platelets with immune cells in SSc are less clearly understood. Platelets are known sources of active pro-inflammatory mediators like HMGB1, and interestingly increased circulating levels of this prototypic alarmin have been shown to correlate with disease activity in SSc. Moreover evidence is growing about the prominent role of circulating heterotypic aggregates (between platelets and innate immune cells) in the pathogenesis of inflammatory and vascular diseases and recent studies are currently evaluating their impact in the pathogenesis of SSc. Furthermore other studies suggested the existence of a specific network between collagen-reactive T lymphocyte and platelets in SSc. In this latter setting platelet activation would be enhanced by the release of IFNγ and a wider array of cytokines from autoreactive T lymphocyte, which in turn would affect megakaryocyte maturation and platelet basal activation state.
Mentions: Several studies have revealed an increased responsiveness of SSc platelets to 5-hydroxytryptamine (5HT), adrenaline, ADP, and collagen (Friedhoff et al., 1984; Goodfield et al., 1988; Postlethwaite and Chiang, 2007). More recently SSc platelets were shown to upregulate a specific non-integrin receptor for type I collagen (Chiang et al., 2006). Type I collagen is in turn abundantly expressed in (injured) vessel walls and is one of the main constituent of fibrotic tissues in SSc. Overexpression of the non-integrin receptor for collagen I together with enhanced downstream signaling ultimately leads to further pro-coagulant activation of platelets, which undergo extensive cytoskeletal remodeling and mobilization of intracellular calcium (Postlethwaite and Chiang, 2007; Figure 1).

Bottom Line: Systemic sclerosis (SSc) is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia.Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target.Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including SSc.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milano, Italy.

ABSTRACT
Systemic sclerosis (SSc) is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia. Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target. Platelets show a unique biological behavior, lying at the crossroads between vascular function, innate and adaptive immunity, and regulation of cell proliferation. Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including SSc. In the setting of SSc platelets are detectable in a persistent activated state, which is intimately linked to the concomitant presence of an injured endothelium and to the widespread activation of the innate and adaptive immune system. As a consistent circulating source of bioactive compounds platelets contribute to the development of many characteristic phenomena of SSc, such as fibrosis and impaired vascular tone.

No MeSH data available.


Related in: MedlinePlus