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Laboratory coagulation assays
Published in John Edward Boland, David W. M. Muller, Interventional Cardiology and Cardiac Catheterisation, 2019
The tests available in the Multiplate system are: ADPtest. Measures platelet aggregation in the presence of adenosine diphosphate (ADP). Sensitive to ADP receptor defects and P2Y12 inhibitors such as clopiodgrel and prasugrel.ADPtest HS. A high-sensitivity measure of the ADP P2Y12 pathway through addition of prostaglandin E2.ASPItest. Measures platelet aggregation in the presence of arachidonic acid. Sensitive to aspirin.TRAPtest. Measures platelet aggregation in the presence of a thrombin receptor activating peptide (platelet PAR1 thrombin receptor). Antiplatelet agents such as aspirin and clopidogrel have little effect on this assay.COLtest. Measures platelet aggregation in the presence of collagen. Sensitive to collagen receptor defects.RISTOtest high and low. Measures platelet aggregation/agglutination in the presence of high and low concentrations of ristocetin. Used to diagnose von Willebrand disease.
Internalization of Microbial Pathogens by Integrin Receptors and the Binding of the Yersinia pseudotuberculosis Invasin Protein
Published in Yoshikazu Takada, Integrins: The Biological Problems, 2017
The bacteria cited above utilize adhesion to ECM components for somewhat unrelated reasons. For Gram-positive cocci, such as S. aureus and Streptococci, it can be argued that ECM binding is irrelevant to microbial adhesion to host cells and, furthermore, is actually a tactic that allows the microbe to avoid undesired contact with cells such as phagocytes. Invasive diseases by S. aureus are associated with abscess formation and colonization of fibrin-rich deposits in the host. Within these sites of heavy ECM deposition, the bacteria can become entrapped and find a niche protected from immune-reactive cells. An additional site of colonization of these microorganisms is within joint tissue, especially in the presence of prosthetic devices.6 The microorganisms could colonize within cartiledge, in such cases, by adhering to ECM components in these sites. A role for the S. aureus collagen receptor has been proposed in this type of colonization, and experimental support exists for this hypothesis.27
Collagens of Normal and Diseased Blood Vessel Wall
Published in Marcel E. Nimni, Collagen, 1988
Adhesion of cells to a collagenous substratum may involve the participation of an intermediary adhesive protein such as fibronectin or laminin51 or may alternatively be effected by direct interaction between the collagen in question and a collagen receptor on the cell surface.52,53 Evidence has been presented that smooth muscle cells bind to interstitial collagens by a fibronectin-dependent mechanism, but that their attachment to collagen type V involves direct interaction with a protein in the cell membrane.53,54 Endothelial cells have been reported to attach to collagen type IV through the mediation of laminin.55 Laminin is synthesized by endothelial cells56 and the ability of these cells to adhere to a laminin-coated surface has been demonstrated.57 However, other studies have emphasized the involvement of fibronectin in the attachment of endothelial cells to a collagenous matrix.47,54,59
How can platelet proteomics best be used to interrogate disease?
Published in Platelets, 2023
For better detection of PTMs with bottom-up analyses, affinity enrichment of the respective PTM is recommended, for example, the enrichment of phosphopeptides from a platelet sample. Likewise the phosphoproteome of the GPVI/ITAM pathway,23,24 cAMP25 and cGMP system26 are extensively studied as well as from patients and with the Scott syndrome27 and in obesity.28 These approaches are well suited to look deeper and more precisely into the respective pathways of platelet reactivity regulation. For example, analysis of phosphopeptide profiles in obese subjects suggested a possible alteration in signaling pathways mediated by platelet Src family kinases. To elucidate this further mechanistically, it could be shown that the collagen receptor GPVI is increasingly present on the surface of the platelets of these patients and their platelets have an increased adhesion to collagen.28
Evolution of platelet activation parameters during septic shock in intensive care unit
Published in Platelets, 2022
Fanny Vardon-Bounes, Cédric Garcia, Alexandra Piton, Jennifer Series, Marie-Pierre Gratacap, Michaël Poëtte, Thierry Seguin, Laure Crognier, Stéphanie Ruiz, Stein Silva, Jean-Marie Conil, Vincent Minville, Bernard Payrastre
The basal level of platelet membrane exposure of CD62P (P-selectin), a marker of α-granule secretion, and CD63, a marker of dense granule secretion was low, both in the control group and in the sepsis group (H0 or H48) (Figure 3a,b). Soluble markers of platelet activation are surrogate of a platelet activation that already happened in patients. As shown Figure 4a, the plasma level of a reliable soluble biomarker of platelet activation, soluble GPVI (sGPVI) shed from the platelet membrane, significantly increased in the sepsis group (H0: 256.5 [155.3–324.4] ng/ml and H48: 253.7 [90.2–336] ng/ml) compared to the control group (48.9 [36.6–71.6] ng/ml, p < .0001 and p = .0001, respectively). The shedding of this collagen receptor was detected at admission and the plasma level of sGPVI was still significantly elevated 48 hours later. Consistent with these results, another plasmatic biomarker of platelet activation, the soluble CD40 ligand (sCD40L), was also increased in the septic group compared to the control group (3.05 [2.1–5.5] ng/ml for sepsis H0, 3.3 [1.9–6.1] ng/ml for sepsis H48 and 1.6 [1.3–2.2] ng/ml for control, p = .0027 and p = .0127, respectively) (Figure 4b).
An evaluation of Ibrutinib for the treatment of Waldenstrom macroglobulinaemia
Published in Expert Opinion on Pharmacotherapy, 2020
Kenneth J. C. Lim, Constantine S. Tam
Ibrutinib is a small molecule that irreversibly binds to Cysteine-481 within the BTK pocket via covalent bonding. This disrupts ATP binding and blocks the phosphorylation and activation of the enzyme, permanently shutting down its signaling capabilities [21]. BTK belongs to the TEC family of non-receptor tyrosine kinases which include other enzymes such as TEC, ITK, BMX, and RLK/TXK [22]. Ibrutinib is not exclusively selective for BTK and has off-target inhibitory activity in other TEC family kinases. These kinases are abundantly expressed in hematopoietic tissue and have major roles in B-cell signaling and T-cell signaling [23,24]. They also have other functions such as in the case of TEC and BTK’s important role in the platelet activation pathway via activation of the collagen receptor glycoprotein VI (GPVI) [25]. Some non-TEC enzymes such as EGFR family kinases, BLK, and JAK3 are also inhibited by Ibrutinib [26]. However, Ibrutinib shows different affinities to these different kinases and has the highest affinity for BTK. This is shown with a low half-maximal inhibitory concentration (IC50) of 0.5 nM for BTK inhibition compared to a IC50 of 78 nM for TEC inhibition [21].