Abstract
Background-Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. Methods and Results-To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14+, indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. Conclusions-This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 379-388 |
| Number of pages | 10 |
| Journal | Circulation: Cardiovascular Genetics |
| Volume | 2 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 2009 |
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Keywords
- Antigens
- Atherosclerosis
- Carotid arteries
- Plaque
- Proteins
- Proteomics
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Genetics(clinical)
- Genetics
- Medicine(all)
Cite this
Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques. / Mayr, Manuel; Grainger, David; Mayr, Ursula; Leroyer, Aurelie S.; Leseche, Guy; Sidibe, Anissa; Herbin, Olivier; Yin, Xiaoke; Gomes, Aldrin V; Madhu, Bassetti; Griffiths, John R.; Xu, Qingbo; Tedgui, Alain; Boulanger, Chantal M.
In: Circulation: Cardiovascular Genetics, Vol. 2, No. 4, 08.2009, p. 379-388.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques
AU - Mayr, Manuel
AU - Grainger, David
AU - Mayr, Ursula
AU - Leroyer, Aurelie S.
AU - Leseche, Guy
AU - Sidibe, Anissa
AU - Herbin, Olivier
AU - Yin, Xiaoke
AU - Gomes, Aldrin V
AU - Madhu, Bassetti
AU - Griffiths, John R.
AU - Xu, Qingbo
AU - Tedgui, Alain
AU - Boulanger, Chantal M.
PY - 2009/8
Y1 - 2009/8
N2 - Background-Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. Methods and Results-To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14+, indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. Conclusions-This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.
AB - Background-Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. Methods and Results-To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14+, indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. Conclusions-This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.
KW - Antigens
KW - Atherosclerosis
KW - Carotid arteries
KW - Plaque
KW - Proteins
KW - Proteomics
UR - http://www.scopus.com/inward/record.url?scp=77449097603&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77449097603&partnerID=8YFLogxK
U2 - 10.1161/CIRCGENETICS.108.842849
DO - 10.1161/CIRCGENETICS.108.842849
M3 - Article
C2 - 20031610
AN - SCOPUS:77449097603
VL - 2
SP - 379
EP - 388
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
SN - 1942-325X
IS - 4
ER -