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The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes.

Cloutier N, Tan S, Boudreau LH, Cramb C, Subbaiah R, Lahey L, Albert A, Shnayder R, Gobezie R, Nigrovic PA, Farndale RW, Robinson WH, Brisson A, Lee DM, Boilard E - EMBO Mol Med (2012)

Bottom Line: Rather, mpICs display autoantigens vimentin and fibrinogen, and recognition of these targets by anti-citrullinated peptide antibodies contributes to the production of mpICs.Functionally, platelet mpICs are highly pro-inflammatory, eliciting leukotriene production by neutrophils.Taken together, our data suggest a unique role for platelet MPs as autoantigen-expressing elements capable of perpetuating formation of inflammatory ICs.

View Article: PubMed Central - PubMed

Affiliation: Faculté de Médecine de l'Université Laval, Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada.

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MPs are heterogeneous in size and are more abundant in RA compared to PA SFA. Acquisition of fluorescent Sky Blue microspheres of 40–90 nm (mean = 90 nm, in cyan blue), 100–300 nm (mean = 220 nm, in pink), 400–600 nm (mean = 450 nm, in green), 700–900 nm (mean = 840 nm, in blue), 2500–4500 nm (mean = 3200 nm, in violet) diameter on a flow cytometer Canto II modified with a FSC-PMT small particles option. A scale bar ranging from 100 to 3200 nm based on the microsphere sizes (FSC-PMT) is presented and used to determine the relative dimensions of the MPs.B,C. Representative FSC-PMT and SSC portrayals of the Annexin-V+ events detected in RA SF (B) and PA SF (C) revealing the dimension diversity of the MPs. The relative dimensions of the MPs are presented according to size-defined microsphere calibrations. Two major subpopulations (subpop 1 and 2) are detected in RA SF (B) while only one (subpop 1) is observed in PA SF (C) are identified on the graphs.D. Triton sensitivity of the MPs in RA SF detected using Annexin-V labeling presented as % of untreated (control).E. Flow cytometric quantifications of the Annexin-V+ MPs contained in RA and PA SF (n = 23 RA and n = 18 PA ***p = 0.0004). Statistical analyses are presented under the graph. Data are mean ± SEM.
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fig01: MPs are heterogeneous in size and are more abundant in RA compared to PA SFA. Acquisition of fluorescent Sky Blue microspheres of 40–90 nm (mean = 90 nm, in cyan blue), 100–300 nm (mean = 220 nm, in pink), 400–600 nm (mean = 450 nm, in green), 700–900 nm (mean = 840 nm, in blue), 2500–4500 nm (mean = 3200 nm, in violet) diameter on a flow cytometer Canto II modified with a FSC-PMT small particles option. A scale bar ranging from 100 to 3200 nm based on the microsphere sizes (FSC-PMT) is presented and used to determine the relative dimensions of the MPs.B,C. Representative FSC-PMT and SSC portrayals of the Annexin-V+ events detected in RA SF (B) and PA SF (C) revealing the dimension diversity of the MPs. The relative dimensions of the MPs are presented according to size-defined microsphere calibrations. Two major subpopulations (subpop 1 and 2) are detected in RA SF (B) while only one (subpop 1) is observed in PA SF (C) are identified on the graphs.D. Triton sensitivity of the MPs in RA SF detected using Annexin-V labeling presented as % of untreated (control).E. Flow cytometric quantifications of the Annexin-V+ MPs contained in RA and PA SF (n = 23 RA and n = 18 PA ***p = 0.0004). Statistical analyses are presented under the graph. Data are mean ± SEM.

Mentions: After optimizing high sensitivity flow cytometry (hs-FCM) parameters to distinguish small particles (Fig 1A), we assessed size and quantity of MPs in RA. For comparison, the MPs present in psoriatic arthritis (PA) – a disease family not associated with intra-articular ICs and complement consumption – were also examined. Similarly to MPs, ICs can display dimensions ranging from 100 to 1000 nm (Gyorgy et al, 2011a). Further, since it is hypothesized that ICs can interact with multiple MPs to form larger components, we included all particles up to 3500 nm in diameter for our analyses. Interestingly, unlike MPs in PA SF, MPs in RA SF appear highly heterogeneous in size and include two major subpopulations, one exhibiting diameters ranging from ∼100 to ∼300 nm and a second one from ∼700 to ∼3000 nm (Fig 1B and C).


The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes.

Cloutier N, Tan S, Boudreau LH, Cramb C, Subbaiah R, Lahey L, Albert A, Shnayder R, Gobezie R, Nigrovic PA, Farndale RW, Robinson WH, Brisson A, Lee DM, Boilard E - EMBO Mol Med (2012)

MPs are heterogeneous in size and are more abundant in RA compared to PA SFA. Acquisition of fluorescent Sky Blue microspheres of 40–90 nm (mean = 90 nm, in cyan blue), 100–300 nm (mean = 220 nm, in pink), 400–600 nm (mean = 450 nm, in green), 700–900 nm (mean = 840 nm, in blue), 2500–4500 nm (mean = 3200 nm, in violet) diameter on a flow cytometer Canto II modified with a FSC-PMT small particles option. A scale bar ranging from 100 to 3200 nm based on the microsphere sizes (FSC-PMT) is presented and used to determine the relative dimensions of the MPs.B,C. Representative FSC-PMT and SSC portrayals of the Annexin-V+ events detected in RA SF (B) and PA SF (C) revealing the dimension diversity of the MPs. The relative dimensions of the MPs are presented according to size-defined microsphere calibrations. Two major subpopulations (subpop 1 and 2) are detected in RA SF (B) while only one (subpop 1) is observed in PA SF (C) are identified on the graphs.D. Triton sensitivity of the MPs in RA SF detected using Annexin-V labeling presented as % of untreated (control).E. Flow cytometric quantifications of the Annexin-V+ MPs contained in RA and PA SF (n = 23 RA and n = 18 PA ***p = 0.0004). Statistical analyses are presented under the graph. Data are mean ± SEM.
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Related In: Results  -  Collection

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fig01: MPs are heterogeneous in size and are more abundant in RA compared to PA SFA. Acquisition of fluorescent Sky Blue microspheres of 40–90 nm (mean = 90 nm, in cyan blue), 100–300 nm (mean = 220 nm, in pink), 400–600 nm (mean = 450 nm, in green), 700–900 nm (mean = 840 nm, in blue), 2500–4500 nm (mean = 3200 nm, in violet) diameter on a flow cytometer Canto II modified with a FSC-PMT small particles option. A scale bar ranging from 100 to 3200 nm based on the microsphere sizes (FSC-PMT) is presented and used to determine the relative dimensions of the MPs.B,C. Representative FSC-PMT and SSC portrayals of the Annexin-V+ events detected in RA SF (B) and PA SF (C) revealing the dimension diversity of the MPs. The relative dimensions of the MPs are presented according to size-defined microsphere calibrations. Two major subpopulations (subpop 1 and 2) are detected in RA SF (B) while only one (subpop 1) is observed in PA SF (C) are identified on the graphs.D. Triton sensitivity of the MPs in RA SF detected using Annexin-V labeling presented as % of untreated (control).E. Flow cytometric quantifications of the Annexin-V+ MPs contained in RA and PA SF (n = 23 RA and n = 18 PA ***p = 0.0004). Statistical analyses are presented under the graph. Data are mean ± SEM.
Mentions: After optimizing high sensitivity flow cytometry (hs-FCM) parameters to distinguish small particles (Fig 1A), we assessed size and quantity of MPs in RA. For comparison, the MPs present in psoriatic arthritis (PA) – a disease family not associated with intra-articular ICs and complement consumption – were also examined. Similarly to MPs, ICs can display dimensions ranging from 100 to 1000 nm (Gyorgy et al, 2011a). Further, since it is hypothesized that ICs can interact with multiple MPs to form larger components, we included all particles up to 3500 nm in diameter for our analyses. Interestingly, unlike MPs in PA SF, MPs in RA SF appear highly heterogeneous in size and include two major subpopulations, one exhibiting diameters ranging from ∼100 to ∼300 nm and a second one from ∼700 to ∼3000 nm (Fig 1B and C).

Bottom Line: Rather, mpICs display autoantigens vimentin and fibrinogen, and recognition of these targets by anti-citrullinated peptide antibodies contributes to the production of mpICs.Functionally, platelet mpICs are highly pro-inflammatory, eliciting leukotriene production by neutrophils.Taken together, our data suggest a unique role for platelet MPs as autoantigen-expressing elements capable of perpetuating formation of inflammatory ICs.

View Article: PubMed Central - PubMed

Affiliation: Faculté de Médecine de l'Université Laval, Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada.

Show MeSH
Related in: MedlinePlus