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PMID: 18509085 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Expression, activation, and function of integrin alphaMbeta2 (Mac-1) on neutrophil-derived microparticles.

Blood ·Vol. 112 ·No. 6 ·2008-09-15 ·Pages 2327-35

Pluskota E, Woody NM, Szpak D, Ballantyne CM, Soloviev DA, Simon DI, Plow EF

Abstract

Leukocyte-derived microparticles (MPs) are markers of cardiovascular diseases and contribute to pathogenesis by their interaction with various cell types. The presence and activation state of a multifunctional leukocyte receptor, integrin alpha(M)beta(2) (CD11b/18), on MPs derived from human neutrophils (PMNs) were examined. alpha(M)beta(2) expression was significantly enhanced on MPs derived from stimulated compared with resting PMNs. Furthermore, alpha(M)beta(2) on MPs from stimulated but not resting PMNs was in an activated conformation because it was capable of binding activation-specific monoclonal antibodies (CBRM1/5 and mAb24) and soluble fibrinogen. MPs expressing active alpha(M)beta(2) interacted with and were potent activators of resting platelets as assessed by induction of P-selectin expression and activation of alpha(IIb)beta(3). With the use of function-blocking antibodies and MPs obtained from alpha(M)(-/-)-deficient mice, we found that engagement of GPIbalpha on platelets by alpha(M)beta(2) on MPs plays a pivotal role in MP binding. Platelet activation by MPs occurs by a pathway dependent on Akt phosphorylation. PSGL-1/P-selectin interaction also is involved in the conjugation of MPs to platelets, and the combination of blocking reagents to both alpha(M)beta(2)/GPIbalpha and to PSGL-1/P-selectin completely abrogates MP-induced platelet activation. Thus, cooperation of these 2 receptor/counterreceptor systems regulates the prothrombotic properties of PMN-derived MPs.

MeSH Terms
Animals Biomarkers/analysis,chemistry Humans Macrophage-1 Antigen/genetics,metabolism,physiology Membrane Glycoproteins/metabolism,physiology Mice Mice, Knockout Neutrophils/chemistry,physiology Platelet Activation Protein Binding Protein Conformation
Chemicals
Biomarkers Macrophage-1 Antigen Membrane Glycoproteins P-selectin ligand protein
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Pluskota Elzbieta
Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic, OH 44195, USA.
Woody Neil M
Szpak Dorota
Ballantyne Christie M
Soloviev Dmitry A
Simon Daniel I
Plow Edward F
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2007-12-127183
Published
2008-09-15
Epub
2008-00-28
Pages
2327-35
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2532806
Subset
IM
Grants
NHLBI NIH HHS · R37 HL057506 · United States
NHLBI NIH HHS · H1 P50 HL 081011 · United States
NHLBI NIH HHS · P50 HL081011 · United States
NHLBI NIH HHS · R01 HL017964 · United States
NHLBI NIH HHS · H1 P50 HL17964 · United States
Corrections
CommentIn
PMID: 18779396
External Links
PubMed source DOI: 10.1182/blood-2007-12-127183 PMC Full Text View journal details
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