Dataset Information

Signaling Pathways of Receptors Involved in Platelet Activation and Shedding of These Receptors in Stored Platelets.

ABSTRACT: All cells encounter various signals coming from the surrounding environment and they need to receive and respond to these signals in order to perform their functions. Cell surface receptors are responsible for signal transduction .Platelets are blood cells which perform several functions using diverse receptors. Platelet concentrate is one of the most consumed blood products. However, due to the short lifespan of the platelets and platelets damage during storage, we face shortage of platelet products. One of the damages that platelets undergo during storage is the loss of surface receptors. Since cell surface receptors are responsible for all cell functions, the loss of platelet receptors reduces the quality of platelet products. In this study, we reviewed the important receptors involved in platelet activation and their associated signaling pathways. We also looked at the platelet receptors that shed during storage and the causes of this incident. We found that GPIbα, P-selectin, CD40 and GPVI are platelet receptors that fall during platelet storage at room temperature. Considering that GPVI and GPIbα are the most important receptors which involved in platelet activation, their shedding can cause decrease in platelet activation after transfusion and decrease thrombus consistence. Shear stress and platelet contact with the container wall are among the mechanisms discussed in this process, but studies in this area have to be continued.

SUBMITTER: Amelirad A

PROVIDER: S-EPMC6468227 | biostudies-other | 2019 Feb

REPOSITORIES: biostudies-other

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Signaling Pathways of Receptors Involved in Platelet Activation and Shedding of These Receptors in Stored Platelets.

Amelirad Asra A Shamsasenjan Karim K Akbarzadehlaleh Parvin P Pashoutan Sarvar Davoud D

Advanced pharmaceutical bulletin 20190221 1

All cells encounter various signals coming from the surrounding environment and they need to receive and respond to these signals in order to perform their functions. Cell surface receptors are responsible for signal transduction .Platelets are blood cells which perform several functions using diverse receptors. Platelet concentrate is one of the most consumed blood products. However, due to the short lifespan of the platelets and platelets damage during storage, we face shortage of platelet pro ...[more]

PMID: 31011556

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Project description:Activation of platelets by exposed collagen after vessel wall injury is a primary event in the pathogenesis of stroke and myocardial infarction. Two collagen receptors, integrin alpha2beta1 and glycoprotein VI (GPVI), are expressed at similar levels on human and mouse platelets, but their individual roles during collagen activation remain poorly defined. Recent genetic and pharmacologic experiments have revealed an essential role for GPVI but have failed to define the role of alpha2beta1 or explain how two structurally distinct collagen receptors might function together to mediate platelet collagen responses. Discriminating the roles of these two collagen receptors is complicated by evidence suggesting that GPVI and platelet integrins may activate a common intracellular signaling pathway. To determine how alpha2beta1 and GPVI activate platelets in response to collagen, we have (i) examined collagen signaling conferred by expression of these receptors in hematopoietic cell lines; (ii) determined the effect of blocking each receptor on the activation of human platelets by collagen; (iii) generated low-GPVI mice in which the alpha2beta1/GPVI receptor ratio has been altered from 1:1 to 50:1 to expose alpha2beta1 function; (iv) studied the collagen responses of mouse platelets lacking LAT, an adaptor protein critical for GPVI but not integrin signaling; and (v) addressed the mechanism by which soluble collagens activate wild-type platelets. These studies demonstrate that alpha2beta1 requires inside-out signals to participate in collagen signaling and that alpha2beta1 is required for collagen activation of platelets when GPVI signals are reduced by blocking anti-GPVI antibody, low receptor number, specific disruption of the GPVI signaling pathway, or forms of collagen that bind weakly to GPVI relative to alpha2beta1. We propose a reciprocal two-receptor model of collagen signaling in platelets in which the nonintegrin receptor GPVI provides the primary collagen signal that activates and recruits the integrin receptor alpha2beta1 to further amplify collagen signals and fully activate platelets through a common intracellular signaling pathway. This model explains many of the genetic and pharmacologic observations regarding collagen signaling in platelets and demonstrates a novel mechanism by which hematopoietic cells integrate signaling by structurally distinct receptors that share a common ligand.

Project description:IntroductionRefrigeration of platelets is considered to provide advantages in therapy of acute hemorrhage due to increased platelet responsiveness. The alleviation of inhibitory signaling caused by cold temperature (CT) has been identified as an important mechanism contributing to enhanced platelet reactivity, detectable in freshly prepared platelets within 1 h of cold storage. The aim of this study was to confirm the effects of short-term refrigeration in platelets from apheresis-derived platelet concentrates (APC).MethodsAPC were stored under standardized conditions for 1 day or for 2 days at room temperature and then refrigerated for 1 h, followed by sampling of platelets for analysis. Platelet reactivity was measured by aggregation studies using threshold concentrations of different agonists and by detection of fibrinogen binding using flow cytometry. The exploration of inhibitory signaling comprised the detection of VASP phosphorylation using flow cytometry or Western blot and the measurement of cyclic nucleotide levels.ResultsAggregation responses induced with ADP, collagen, or thrombin receptor-activating peptide-6 (TRAP-6) were increased in APC after cold storage for 1 h, associated with elevated TRAP-6-induced fibrinogen binding. VASP phosphorylation levels were decreased after cold exposition, detectable in 1-day- and 2-day-stored APC with flow cytometry, and in 2-day-stored APC with Western blot technique. Induced cGMP levels were lower after storage at CT in APC on day 1 and on day 2, whereas cAMP levels were reduced on 2-day-stored APC.ConclusionShort-term refrigeration for 1 h is sufficient to induce an attenuation of inhibitory signaling, accompanied with increased aggregation responses in APC stored for up to 2 days. The "on demand" refrigeration of PC may be a reasonable approach for the preparation of platelets with enhanced responsiveness to treat patients with hemorrhage more effectively, which should be further addressed in consecutive studies.

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Dataset Information

Signaling Pathways of Receptors Involved in Platelet Activation and Shedding of These Receptors in Stored Platelets.

Publications

Signaling Pathways of Receptors Involved in Platelet Activation and Shedding of These Receptors in Stored Platelets.

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