Platelets can enhance vascular permeability

Abstract

<jats:title>Abstract</jats:title><jats:p>Platelets survey blood vessels, searching for endothelial damage and preventing loss of vascular integrity. However, there are circumstances where vascular permeability increases, suggesting that platelets sometimes fail to fulfill their expected function. Human inflammatory arthritis is associated with tissue edema attributed to enhanced permeability of the synovial microvasculature. Murine studies have suggested that such vascular leak facilitates entry of autoantibodies and may thereby promote joint inflammation. Whereas platelets typically help to promote microvascular integrity, we examined the role of platelets in synovial vascular permeability in murine experimental arthritis. Using an in vivo model of autoimmune arthritis, we confirmed the presence of endothelial gaps in inflamed synovium. Surprisingly, permeability in the inflamed joints was abrogated if the platelets were absent. This effect was mediated by platelet serotonin accumulated via the serotonin transporter and could be antagonized using serotonin-specific reuptake inhibitor antidepressants. As opposed to the conventional role of platelets to microvascular leakage, this demonstration that platelets are capable of amplifying and maintaining permeability adds to the rapidly growing list of unexpected functions for platelets.</jats:p>

Platelets in Early Antibody-Mediated Rejection of Renal Transplants

“…47 Platelets can also fragment into microparticles that deliver mediators to neighboring cells. 42,48 Finally, platelets are phagocytized by macrophages. In all of these mechanisms, intact platelets disappear but are instrumental in the process of perpetuating inflammation.…”

“…40 More recently, the increased vascular permeability caused by platelet-derived serotonin has been found to be a critical step in the inflammatory lesions of rheumatoid arthritis and lupus. 41,42 More prolonged effects of serotonin include the induction of fibrotic responses. 43 In conjunction with the release of chemokines, the expression of P-selectin on activated platelets promotes interactions with macrophages.…”

Blood cells and endothelial barrier function

“…116 Platelets and endothelial barrier function Recently, much attention has been devoted to addressing the role of platelets in inflammation, and the evolving consensus is that platelets tend to amplify diffrent components of the inflammatory response, most notably the expression of endothelial cell adhesion molecules and the recruitment of leukocytes. 117,118 While there are some reports that describe the ability of platelets to diminish endothelial barrier function, 119 there is a larger body of evidence that supports an anti-permeability effect of platelets. 120 For example, thrombocytopenia appears to elicit an increased vascular permeability in resting microvessels and this response is reversed following the restoration of blood platelet count.…”

Platelet and red blood cell interactions and their role in rheumatoid arthritis

“…They are also capable of post-translational automodification of their mRNAs following release from megakaryocytes via activation by molecular signals common to oxidative or haemostatic pathways [67]. They enhance vascular permeability and release MPs, which have been implicated in aiding the formation of immune complexes via autoantigen expression [68,69]. MPs were also found to be carriers of the C-type lectin-like receptor 2 (CLEC-2) as with the originating cells which enables cleavage of the platelet glycoprotein GPVI [70].…”