Anti-β2 Glycoprotein I Antibodies Cause Inflammation and Recruit Dendritic Cells in Platelet Clearance

Bondanza, Attilio; Manfredi, Angelo A.; Zimmermann, Valérie S.; Iannacone, Matteo; Tincani, Anǵela; Balestrieri, G.; Sabbadini, Maria Grazia; Querini, Patrizia Rovere

doi:10.1055/s-0037-1616059

Cited by 8 publications

(6 citation statements)

References 39 publications

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“…Interestingly, the treatment was effective at inducing the development of anti‐β 2 GPI antibodies in both autoimmune‐prone and normal mice (Figure 4). Further experiments will be necessary to verify whether other particulate substrates that expose phosphatidylserine (63, 64) are an equally efficient source of β 2 GPI for crosspresentation in vivo.…”

Section: Discussionmentioning

confidence: 99%

Requirement of dying cells and environmental adjuvants for the induction of autoimmunity

Bondanza¹,

Zimmermann²,

Dell’Antonio³

et al. 2004

Arthritis & Rheumatism

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Section: Discussionmentioning

confidence: 99%

Requirement of dying cells and environmental adjuvants for the induction of autoimmunity

Bondanza¹,

Zimmermann²,

Dell’Antonio³

et al. 2004

Arthritis & Rheumatism

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“…27 Results were expressed as the percentage of annexin A5 ϩ events in the whole CD61 ϩ platelet For personal use only. on May 12, 2018. by guest www.bloodjournal.org From population.…”

Section: Activation Of Platelets and Neutrophilsmentioning

confidence: 99%

“…27 Results were expressed as the percentage of annexin A5 ϩ events in the whole CD61 ϩ platelet population. To determine P-selectin expression, platelets were simultaneously fixed (Thrombofix 18 ), labeled with FITC-conjugated mAb against CD61 and PE-conjugated against P-selectin, and analyzed by flow cytometry in purified platelet suspensions as well as in whole-blood samples.…”

Section: Activation Of Platelets and Neutrophilsmentioning

confidence: 99%

Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and β2 integrin–dependent cell clearance program

Maugeri

Rovere‐Querini

Evangelista

et al. 2009

Blood

131

153

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Activated platelets express ligands, which are recognized by counterreceptors on neutrophils. Here, we show that the ensuing cell-to-cell interaction programs neutrophil phagocytic function, resulting in activated platelet clearance. Neutrophils that have internalized platelets circulate in the blood of patients with acute myocardial infarction, and the extent of platelet clearance correlates with expression of platelet activation, including P-selectin. Activated platelets injected intravenously in experimental animals are detectable in circulating neutrophils 60 minutes after, and within 3 hours, more than 70% circulating neutrophils have internalized platelets. Platelet clearance comprises 2 events: adhesion to neutrophils, which requires divalent cations and depends on P-selectin, on the P-selectin glycoprotein ligand-1 (PSGL-1), and on the CD11b/CD18 ␤2 integrin; and internalization, which is abrogated by the phosphatidylserine-binding protein annexin A5. Adhesion to platelets causes neutrophil degranulation and is blocked by antibodies specific for P-selectin and PSGL-1, either in a synthetic medium in vitro or in the whole blood, therefore in the presence of a physiologic array of plasma cofactors and opsonins. The data suggest that the interaction between circulating platelets and neutrophils influences innate immune functions, possibly contributing to regulate vascular inflammation. IntroductionNeutrophils are recruited to inflamed sites, where they are required for microbial clearance. Neutrophil recruitment is a multistep process, which comprises initial tethering and rolling along the vessel wall, firm adhesion to endothelial cells, and eventual extravasation. It involves consecutively various adhesion molecules, including selectins and ␤2 integrins. [1][2][3][4] Granules of endothelial cells (Weibel-Palade bodies) and of platelets (␣-granules) contain P-selectin. Inflammatory stimuli cause its translocation at the endothelial cell surface. The interaction with the counterreceptor, PSGL-1, prompts leukocyte tethering and rolling and initiates the second phase of the process, firm adhesion. During these events, integrins shift to an active conformation. [5][6][7] Integrin activation depends on the signaling cascade downstream the P-selectin/PSGL-1 interaction. [8][9][10] Platelets adhere and are activated at sites of vascular injury: there, they produce a releasate, some contents of which penetrate and/or interact biochemically with neutrophils. This includes unprocessed free arachidonic acid which can then be transformed into leukotriene A4 and B4. 11-14 Furthermore, activated platelets express P-selectin. Platelet P-selectin guarantees the access of leukocytes to perivascular tissues even when dying or severely damaged endothelial cells fail to sustain leukocyte rolling and adhesion. 15,16 Indeed, endothelial cells surrounding the lesion release signals that amplify the expression of P-selectin on adhering platelets. 17 The P-selectin-dependent interaction of neutrophils and platelets amplifies mut...

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“…By analysing the proteins that associate with the liposomes in blood, Chonn et al identified β2-glycoprotein I as a major protein associated with rapidly cleared liposomes and noted that pretreating the mice with anti-β2-glycoprotein I antibodies significantly increased the half-life of the liposomes (26). In vitro, β2-glycoprotein I was also shown to promote the phagocytosis of phosphatidylserine containing liposomes, activated platelets (8,27,28) and apoptotic tumour cells (29). In conditions associated with increased microvesicles generation such as disseminated intravascular coagulation, plasma levels of β2-glycoprotein I was reduced presumably due to its consumption (30).…”

Section: Discussionmentioning

confidence: 99%

Phagocytosis of platelet microvesicles and β2– glycoprotein I

Abdel-Monem

Dasgupta²,

Le³

et al. 2010

Thromb Haemost

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The majority of the antiphospholipid antibodies, present in patients with antiphospholipid syndrome, are directed against conformational epitopes in beta2-glycoprotein I. beta2-glycoprotein I is an anionic phospholipid-binding 50-kDa plasma protein whose physiological role is not clear. Here we investigate the role of beta2-glycoprotein I in the phagocytosis of phosphatidylserine-expressing platelet microvesicles and the effect of autoantibodies to beta2-glycoprotein I on this process. We labelled the glycans of beta2-glycoprotein I with BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene)-hydrazide without affecting its phospholipid binding capacity. BODIPY-beta2-glycoprotein I bound to platelet microvesicles in a concentration-dependent manner and promoted the phagocytosis of platelet microvesicles by THP-1 derived macrophages in vitro at physiological plasma concentrations with a half maximal effect at approximately 10 microg/ml. beta2-glycoprotein I-stimulated phagocytosis was inhibited by annexin A5 and the phosphatidylserine-binding C1C2 fragment of lactadherin. Furthermore, immunoaffinity purified beta2-glycoprotein I-dependent antiphospholipid antibodies from five patients with antiphospholipid syndrome inhibited the phagocytosis in a concentration-dependent manner. These studies suggest that the binding of beta2-glycoprotein I to phosphatidylserine-expressing procoagulant platelet microvesicles may promote their clearance by phagocytosis and autoantibodies to beta2-glycoprotein I may inhibit this process to induce a procoagulant state.

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Anti-β2 Glycoprotein I Antibodies Cause Inflammation and Recruit Dendritic Cells in Platelet Clearance

Cited by 8 publications

References 39 publications

Requirement of dying cells and environmental adjuvants for the induction of autoimmunity

Requirement of dying cells and environmental adjuvants for the induction of autoimmunity

Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and β2 integrin–dependent cell clearance program

Phagocytosis of platelet microvesicles and β2– glycoprotein I

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