Physical proximity and functional interplay of PECAM-1 with the Fc receptor FcγRIIa on the platelet plasma membrane

Thai, Le M.; Ashman, Leonie K.; Harbour, Stacey N.; Hogarth, P. Mark; Jackson, Denise E.

doi:10.1182/blood-2003-02-0496

Cited by 47 publications

(38 citation statements)

References 42 publications

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“…At least in platelets, CD31 associates with Fc␥RIIa, which is down-regulated by crosslinking anti-CD31 monoclonal antibody (40) and may therefore interfere with Fc␥RIIa-mediated uptake of RNAcontaining ICs in PDCs. Another possibility is that anti-CD31 monoclonal antibody acts by blocking homophilic or heterophilic interactions between B cells and PDCs.…”

Section: Discussionmentioning

confidence: 99%

B lymphocytes enhance interferon‐α production by plasmacytoid dendritic cells

Berggren¹,

Hagberg²,

Weber³

et al. 2012

Arthritis & Rheumatism

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Objective. The type I interferon (IFN) system and B cells are activated in many autoimmune diseases, such as systemic lupus erythematosus (SLE). The IFN␣ produced by plasmacytoid dendritic cells (PDCs) stimulates several B cell functions, including autoantibody production. However, not much is known about how B cells influence PDC function. The aim of this study was to investigate the regulatory effect of B cells on IFN␣ production by PDCs.Methods. PDCs and B cells isolated from peripheral blood mononuclear cells from healthy blood donors were stimulated with RNA-containing immune complexes (ICs) consisting of U1 small nuclear RNP and SLE IgG, herpes simplex virus, or oligonucleotide (ODN) 2216, alone or in cocultures. IFN␣, several other cytokines, and PDC-or B cell-associated surface molecules were analyzed using immunoassays or flow cytometry.Results. B cells enhanced IFN␣ production by PDCs up to 47-fold, and the effect was most pronounced for PDCs stimulated with RNA-containing ICs. Anti-CD31 antibody reduced RNA-containing IC-induced IFN␣ production by 80% but had no effect on IFN␣ production when ODN 2216 was used as an inducer. Supernatants from ODN 2216-stimulated B cells promoted IFN␣ production by PDCs, while supernatants from RNA-containing IC-stimulated B cells did not.Conclusion. Our results showed that a novel function of B cells is enhancement of type I IFN production by PDCs. Because B cells are activated by type I IFN, this PDC-B cell cross-talk might be of fundamental importance in the etiopathogenesis of SLE and contribute to long-term immune activation in SLE and other systemic rheumatic diseases.

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Section: Discussionmentioning

confidence: 99%

B lymphocytes enhance interferon‐α production by plasmacytoid dendritic cells

Berggren¹,

Hagberg²,

Weber³

et al. 2012

Arthritis & Rheumatism

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“…In addition, FcγRIIA has been shown to stimulate platelets through interaction with other molecules and receptors, including α2bβ3, GP1b-IX-V and von Willebrand factor [25][26][27]. Furthermore, FcγRIIA and PECAM-1 are physically and functionally associated on the surface of human platelets [28]. Human platelets have been shown to internalize IgG-containing immune complexes, abundant during malaria infection, and polymorphisms in FcγRIIA have been implicated in susceptibility to severe malaria [24,29].…”

Section: A Spoonful Of Antibodies Makes the Platelets Go Down?mentioning

confidence: 99%

Platelet power: sticky problems for sticky parasites?

Pleass

2009

Trends in Parasitology

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Platelets might have a crucial role in the pathogenesis of both human and rodent malarias by assisting in the sequestration of infected erythrocytes within the cerebral vasculature. However, recent elegant work by McMorran et al. suggests that they are also involved in innate protection during the early stages of infection. Here, we discuss the implications of their important findings in the context of immunity to malaria. Platelet: friend or foe?The platelet, traditionally known for its role in blood clotting, is also known for its putative involvement in malaria pathology [1,2]. However, a recent study using C57BL6 mice genetically deficient in the megakaryocyte growth and differentiation factor C-mpl (encoded by the Mpl gene), and resulting in mice with 90% fewer platelets, showed that these animals were significantly more susceptible to death when infected with Plasmodium chabaudi [3]. Furthermore, the authors went on to show that purified human platelets killed Plasmodium falciparum parasites within red blood cells when added to in vitro cultures and that various platelet antagonists, including aspirin, reversed this antiparasitic activity both in vitro and in vivo. This result raises concerns over the use of aspirin as an antipyretic in patients with malaria. Using specific receptor antagonists, the authors demonstrated that killing and control of parasite growth in P. falciparum cultures was dependent on platelet activation via P2Y1, an ADP-dependent metabotrophic puronergic receptor (Figure 1).These results in animals seem counterintuitive, in that platelets are believed to be involved in pathological disease states that hasten death, such as cerebral malaria [1,2]. For example, mice with significantly compromised platelet function (CXCL4 or CXCR3 deficient) have been shown to survive longer than their wild-type counterparts [4]. By contrast, platelet depletion by anti-CD41 monoclonal antibody injection early, but not late, in the course of disease is known to protect C57BL6 mice from Plasmodium berghei ANKA-induced severe experimental cerebral malaria (ECM) by altering levels of pathogenic cytokines [5]. Unfortunately, the study by McMorran et al. used P. chabaudi, a rodent malaria thatalthough capable of sequestering to a number of organs -is not known to develop ECM. It should also be noted that non-sequestering Plasmodium species also give rise to ECM in some inbred mouse strains, Plasmodium yoelii 17XL in BALB/c mice being a good example Europe PMC Funders Group A cornucopia of receptorsThe first of these questions is easier to explain for P. falciparum than for Plasmodium vivax or the murine malarias. Platelet-mediated clumping is common in P. falciparum field isolates, is distinctive from other adhesive phenotypes and involves the host receptors CD36[7] and gC1qR/HABP1/p32 [8]. Whether these are the only platelet receptors involved is debatable and worth exploring. Although GPIIb/IIIa (CD41/CD61) and GPIb/IX (CD42a/ CD42b)-deficient platelets still clump to infected erythrocytes [7], the...

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“…PECAM-1 also inhibits GPIb-mediated platelet activation (Rathore et al, 2003) and downregulates FcγRIIA-mediated platelet responses (Thai et al, 2003). The effects of PECAM-1 appear not to be restricted to inhibition of ITAM-mediated signalling: thrombin-dependent and oxidized low-density lipoprotein (LDL)-stimulated platelet signalling are also inhibited (Cicmil et al, 2002;Relou et al, 2003).…”

Section: Integrin Signallingmentioning

confidence: 99%

“…The protein tyrosine phosphatases Shp-1 and Shp-2 and the serine/threonine protein phosphatase PP2A associate with PECAM-1 in platelets (Jackson et al, 1997b;Relou et al, 2003). Although PECAM-1 signalling reduces total platelet protein tyrosine phosphorylation, inositol phosphate production, calcium mobilization and PI3K signalling (Cicmil et al, 2002;Jones et al, 2001;Thai et al, 2003), specific substrates for these phosphatases in platelets are currently unclear.…”

Section: Integrin Signallingmentioning

confidence: 99%

Platelet adhesion signalling and the regulation of thrombus formation

Gibbins

2004

Journal of Cell Science

259

232

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Platelets perform a central role in haemostasis and thrombosis. They adhere to subendothelial collagens exposed at sites of blood vessel injury via the glycoprotein (GP) Ib-V-IX receptor complex, GPVI and integrin α2β1. These receptors perform distinct functions in the regulation of cell signalling involving non-receptor tyrosine kinases (e.g. Src, Fyn, Lyn, Syk and Btk), adaptor proteins, phospholipase C and lipid kinases such as phosphoinositide 3-kinase. They are also coupled to an increase in cytosolic calcium levels and protein kinase C activation, leading to the secretion of paracrine/autocrine platelet factors and an increase in integrin receptor affinities. Through the binding of plasma fibrinogen and von Willebrand Factor to integrin αIIbβ3, a platelet thrombus is formed. Although increasing evidence indicates that each of the adhesion receptors GPIb-V-IX and GPVI and integrins α2β1 and αIIbβ3 contribute to the signalling that regulates this process, the individual roles of each are only beginning to be dissected. By contrast, adhesion receptor signalling through platelet endothelial cell adhesion molecule 1 (PECAM-1) is implicated in the inhibition of platelet function and thrombus formation in the healthy circulation. Recent studies indicate that understanding of platelet adhesion signalling mechanisms might enable the development of new strategies to treat and prevent thrombosis.

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Physical proximity and functional interplay of PECAM-1 with the Fc receptor FcγRIIa on the platelet plasma membrane

Cited by 47 publications

References 42 publications

B lymphocytes enhance interferon‐α production by plasmacytoid dendritic cells

B lymphocytes enhance interferon‐α production by plasmacytoid dendritic cells

Platelet power: sticky problems for sticky parasites?

Platelet adhesion signalling and the regulation of thrombus formation

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