Functional expression of IgA receptor FcαRI on human platelets

Qian, Kun; Xie, Fenglong; Gibson, Andrew; Edberg, Jeffrey C.; Kimberly, Robert P.; Wu, Jianming

doi:10.1189/jlb.0508327

Cited by 57 publications

(49 citation statements)

References 64 publications

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“…34 -37,55 -59 Expression has recently been described on human platelets as well, whereas Fc RI is not expressed on mast cells or basophils. 60 Fc RI expression is constitutive and independent of its ligand, which is demonstrated in IgA-deficient patients who still express Fc RI. 61 However, depending on the cell type, expression and function of Fc RI can be modulated by lipopolysaccharide, chemoattractants, inflammatory cytokines, or adapter protein, binding to the intracellular domain of Fc RI.…”

Section: Expression and Modulationmentioning

confidence: 97%

The human immunoglobulin A Fc receptor FcαRI: a multifaceted regulator of mucosal immunity

2011

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Immunoglobulin A (IgA) is commonly recognized as the most prevalent antibody (Ab) at mucosal sites with an important role in defense by shielding mucosal surfaces from invasion by pathogens. However, its potential to both actively dampen excessive immune responses or to initiate potent proinflammatory cellular processes is less well known. Interestingly, either functional outcome is mediated through interaction with the myeloid IgA Fc receptor FcαRI (CD89). Monomeric interaction of IgA with FcαRI triggers inhibitory signals that block activation via other receptors, whereas multimeric FcαRI crosslinking induces phagocytosis, reactive oxygen species production, antigen presentation, Ab-dependent cellular cytotoxicity, and cytokine release. Thus, FcαRI acts as a regulator between anti- and proinflammatory responses of IgA. As such, the biology of FcαRI, and its multifaceted role in immunity will be the focus of this review.

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Section: Expression and Modulationmentioning

confidence: 97%

The human immunoglobulin A Fc receptor FcαRI: a multifaceted regulator of mucosal immunity

2011

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“…There is no evidence that these anucleate cytoplasts undergo cellular division, but recent studies by our group and others have identified unexpected cellular functions of platelets, [2][3][4] including the capacity to process pre-mRNA [2][3][4][5] and translate mRNA into protein. [6][7][8][9][10] Platelets also continue to synthesize protein for several days when they are stored ex vivo.…”

Section: Introductionmentioning

confidence: 97%

Anucleate platelets generate progeny

Schwertz

Köster

Kahr

et al. 2010

Blood

163

176

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Platelets are classified as terminally differentiated cells that are incapable of cellular division. However, we observe that anucleate human platelets, either maintained in suspension culture or captured in microdrops, give rise to new cell bodies packed with respiring mitochondria and ␣-granules. Platelet progeny formation also occurs in whole blood cultures. Newly formed platelets are structurally indistinguishable from normal platelets, are able to adhere and spread on extracellular matrix, and display normal signaldependent expression of surface Pselectin and annexin V. Platelet progeny formation is accompanied by increases in biomass, cellular protein levels, and protein synthesis in expanding populations. Platelet numbers also increase during ex vivo storage. These observations indicate that platelets have a previously unrecognized capacity for producing functional progeny, which involves a form of cell division that does not require a nucleus. Because this new function of platelets occurs outside of the bone marrow milieu, it raises the possibility that thrombopoiesis continues in the bloodstream. (Blood. 2010;115(18):3801-3809) IntroductionAfter they are shed from the cytoplasm of megakaryocytes, 1 platelets circulate in the bloodstream for 9 to 11 days. There is no evidence that these anucleate cytoplasts undergo cellular division, but recent studies by our group and others have identified unexpected cellular functions of platelets, 2-4 including the capacity to process pre-mRNA 2-5 and translate mRNA into protein. [6][7][8][9][10] Platelets also continue to synthesize protein for several days when they are stored ex vivo. 11 These findings indicate that, despite their terminally differentiated state, platelets are biosynthetically more sophisticated than previously thought. 12 They also suggest that platelets may be able to adjust their phenotypic composition in response to environmental cues.Here we show that platelets give rise to new cells that are structurally and functionally similar to their parent counterparts. The formation of platelet progeny is associated with increases in platelet biomass, protein synthetic events, and total intracellular protein. This heretofore undescribed proliferative capacity of platelets may have significant consequences for normal and pathologic thrombopoiesis in humans in addition to having clinical implications for transfusion medicine. Methods Platelet isolation and cultureAll studies were approved by the University of Utah Institutional Review Board committee (no. 392). Leukocyte-depleted platelets were isolated as previously described. 2,5 Washed platelets were resuspended at 100 000/L in serum-free M199 medium, placed in round-bottom polypropylene tubes (BD Biosciences), and cultured in a 37°C humidified incubator under gentle rotation (MacsMix, slow, 45°angle; Miltenyi). The same suspension culture conditions were also used for the whole blood studies shown in Figure 2A.Stored platelets were obtained from the ARUP Blood Transfusion Services at the University o...

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“…Human IgA also plays important roles in the pathogenesis of other phenotypes, including dermatitis herpetiformis, celiac disease, periodontal disease, and IgA nephropathy. The presence of an IgA antibody against ␤ 2 -glycoprotein I has been associated significantly with strokes, extensive and recurrent venous thrombosis, and coincident arterial and venous thrombosis in cancer patients (42). Platelets also express Fc⑀RI and Fc⑀RII, receptors for IgE (23).…”

Section: Discussionmentioning

confidence: 99%

“…Platelet Fc␥RII binds IgG 1 and IgG 3 with more avidity than it binds IgG 2 and IgG 4 (29). In addition, platelets express Fc␣RI (CD89), which constitutively associates with FcR␥ and, when cross-linked, leads to Syk phosphorylation, platelet activation, and the release of tissue factor and interleukin-1␤ (42). Furthermore, auto-antibodies of the IgA isotype have been identified to react with ␤ 2 -glycoprotein I, Ro/SSA, La/SSB, cardiolipin in serum of patients with SLE and Sjogren's syndrome, in the antiphospholipid syndrome, and increased IgA rheumatoid factor (IgA auto-antibodies) was found in RA patients.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Syk activity by R788 in platelets prevents remote lung tissue damage after mesenteric ischemia-reperfusion injury

Lapchak

Kannan

Rani

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Tissue injury following ischemia-reperfusion (I/R) occurs as a consequence of actions of soluble factors and immune cells. Growing evidence supports a role for platelets in the manifestation of tissue damage following I/R. Spleen tyrosine kinase has been well documented to be important in lymphocyte activation and more recently in platelet activation. We performed experiments to evaluate whether inhibition of platelet activation through inhibition of spleen tyrosine kinase prevents tissue damage after mesenteric I/R injury. Platelets isolated from C57BL/6J mice fed with R788 for 10 days were transfused into C57BL/6J mice depleted of platelets 2 days before mesenteric I/R injury. Platelet-depleted mice transfused with platelets from R788-treated mice before mesenteric I/R displayed a significant reduction in the degree of remote lung damage, but with little change in the degree of local intestinal damage compared with control I/R mice. Transfusion of R788-treated platelets also decreased platelet sequestration, C3 deposition, and immunoglobulin deposition in lung, but not in the intestine, compared with control groups. These findings demonstrate that platelet activation is a requisite for sequestration in the pulmonary vasculature to mediate remote tissue injury after mesenteric I/R. The use of small-molecule inhibitors may be valuable to prevent tissue damage in remote organs following I/R injury.

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Functional expression of IgA receptor FcαRI on human platelets

Cited by 57 publications

References 64 publications

The human immunoglobulin A Fc receptor FcαRI: a multifaceted regulator of mucosal immunity

The human immunoglobulin A Fc receptor FcαRI: a multifaceted regulator of mucosal immunity

Anucleate platelets generate progeny

Inhibition of Syk activity by R788 in platelets prevents remote lung tissue damage after mesenteric ischemia-reperfusion injury

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