Galectin‐9 activates platelet ITAM receptors glycoprotein VI and C‐type lectin‐like receptor‐2

Zhi, Zhaogong; Jooss, Natalie J.; Sun, Yi; Colicchia, Martina; Slater, Alexandre; Morán, Luis A.; Cheung, Hilaire Yam Fung; Di, Ying; Rayes, Julie; Poulter, Natalie S.; Watson, Steve P.; Iqbal, Asif

doi:10.1111/jth.15625

Cited by 12 publications

(9 citation statements)

References 69 publications

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“…In addition, the interaction between P-selectin expressed on platelets in response to gal-9 and PSGL-1 (P-selectin glycoprotein ligand-1, CD162) expressed on leukocytes potentially facilitates platelet-leukocyte aggregation causing leukocyte recruitment and inflammation. 47 4. CXCL4 (chemokine [C-X-C motif] ligand 4) released by activated platelets: CXCL4 or PF4 (platelet factor 4) is a platelet specific cytokine, stored in platelet α-granules and released into the plasma in micromolar concentrations following platelet activation.…”

Section: Aggarwal Et Almentioning

confidence: 99%

Section: Platelets and Vascular Remodellingmentioning

confidence: 99%

“…44 Of the 15 known gals identified in mammals, gal-1, gal-3, gal-8, and gal-9 have been shown to interact with platelet surface receptors to cause negative remodeling of the vessel wall through inflammation and atherosclerosis. [44][45][46][47] It has been shown that structurally divergent galectins (gal-1, gal-3, and gal-8) can initiate platelet responses including adhesion, spreading, aggregation, release of granular content, and expression of P-selectin through their interaction with carbohydrate part of platelet receptors GPIb/IX/V complex and integrin α IIb β 3 . 45,48 During vascular injury, platelets adhere to the extracellular matrix and gals interact with GP Ib/IX/V to promote platelet extracellular matrix adhesion.…”

Section: Aggarwal Et Almentioning

confidence: 99%

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Platelets at the Vessel Wall in Non-Thrombotic Disease

Aggarwal

Jennings

Manning

et al. 2023

Circulation Research

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Platelets are small, anucleate entities that bud from megakaryocytes in the bone marrow. Among circulating cells, platelets are the most abundant cell, traditionally involved in regulating the balance between thrombosis (the terminal event of platelet activation) and hemostasis (a protective response to tissue injury). Although platelets lack the precise cellular control offered by nucleate cells, they are in fact very dynamic cells, enriched in preformed RNA that allows them the capability of de novo protein synthesis which alters the platelet phenotype and responses in physiological and pathological events. Antiplatelet medications have significantly reduced the morbidity and mortality for patients afflicted with thrombotic diseases, including stroke and myocardial infarction. However, it has become apparent in the last few years that platelets play a critical role beyond thrombosis and hemostasis. For example, platelet-derived proteins by constitutive and regulated exocytosis can be found in the plasma and may educate distant tissue including blood vessels. First, platelets are enriched in inflammatory and anti-inflammatory molecules that may regulate vascular remodeling. Second, platelet-derived microparticles released into the circulation can be acquired by vascular endothelial cells through the process of endocytosis. Third, platelets are highly enriched in mitochondria that may contribute to the local reactive oxygen species pool and remodel phospholipids in the plasma membrane of blood vessels. Lastly, platelets are enriched in proteins and phosphoproteins which can be secreted independent of stimulation by surface receptor agonists in conditions of disturbed blood flow. This so-called biomechanical platelet activation occurs in regions of pathologically narrowed (atherosclerotic) or dilated (aneurysmal) vessels. Emerging evidence suggests platelets may regulate the process of angiogenesis and blood flow to tumors as well as education of distant organs for the purposes of allograft health following transplantation. This review will illustrate the potential of platelets to remodel blood vessels in various diseases with a focus on the aforementioned mechanisms.

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Section: Aggarwal Et Almentioning

confidence: 99%

Section: Platelets and Vascular Remodellingmentioning

confidence: 99%

Section: Aggarwal Et Almentioning

confidence: 99%

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Platelets at the Vessel Wall in Non-Thrombotic Disease

Aggarwal

Jennings

Manning

et al. 2023

Circulation Research

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“…63,64,65 A high expression of podoplanin has indeed been observed in squamous cell carcinomas. 66 Alongside to podoplanin, also hemin 67 and galectin-9 68 can act as endogenous ligands for mouse and human CLEC-2. Besides these endogenous ligands, CLEC-2 can be activated by the snake venom rhodocytin, to result in rapid platelet activation.…”

Section: The Platelet Clec-2 Receptormentioning

confidence: 99%

“…As indicated above, fibrinogen and fibrin have been identified as novel ligands for the GPVI receptor. 49,50,77,78 In addition, several other ligands have been introduced, including α5-laminin, 79 fibronectin, 80 vitronectin, 81 galectin-9 and galactin-3, 68,82 and very recently the coagulation factor XIII. 83 However, the in vivo implications of the binding to these non-collagen ligands are still under investigation.…”

Section: The Platelet Multiligand Glycoprotein VI Receptormentioning

confidence: 99%

Novel platelet glycoprotein VI and CLEC-2 targeting strategies

Navarro¹

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Glycoprotein (GP)VI is the major platelet collagen receptor and a promising antithrombotic target. This was first demonstrated in mice using the rat monoclonal antibody JAQ1, which completely blocks the collagen-related peptide (CRP)-binding site on mouse GPVI and efficiently inhibits mouse platelet adhesion, activation and aggregation on collagen. Here, we show for the first time that JAQ1 cross-reacts with human GPVI (huGPVI), but not with GPVI in other tested species, including rat, rabbit, guinea pig, swine, and dog. We further demonstrate that JAQ1 differently modulates mouse and human GPVI function. Similar to its effects on mouse GPVI (mGPVI), JAQ1 inhibits CRP-induced activation in human platelets, whereas, in stark contrast to mouse GPVI, it does not inhibit the adhesion, activation or aggregate formation of human platelets on collagen, but causes instead an increased response. This effect was also seen with platelets from newly generated human GPVI knock-in mice (hGP6tg/tg).These results indicate that the binding of JAQ1 to a structurally conserved epitope in GPVI differently affects its function in human and mouse platelets.

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