RGD Reference Report - P-selectin-mediated platelet-neutrophil aggregate formation activates neutrophils in mouse and human sickle cell disease. - Rat Genome Database

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P-selectin-mediated platelet-neutrophil aggregate formation activates neutrophils in mouse and human sickle cell disease.

Authors: Polanowska-Grabowska, R  Wallace, K  Field, JJ  Chen, L  Marshall, MA  Figler, R  Gear, AR  Linden, J 
Citation: Polanowska-Grabowska R, etal., Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2392-9. Epub 2010 Nov 11.
RGD ID: 6219007
Pubmed: PMID:21071696   (View Abstract at PubMed)
PMCID: PMC3058044   (View Article at PubMed Central)

OBJECTIVE: To determine the role of platelets in stimulating mouse and human neutrophil activation and pulmonary injury in sickle cell disease (SCD). METHODS AND RESULTS: Both platelet and neutrophil activation occur in SCD, but the interdependence of these events is unknown. Platelet activation and binding to leukocytes were measured in mice and patients with SCD and in controls. Relative to controls, blood obtained from mice or patients with SCD contained significantly elevated platelet-neutrophil aggregates (PNAs). Both platelets and neutrophils found in sickle PNAs were activated. Multispectral imaging (ImageStream) and conventional flow cytometry revealed a subpopulation of activated neutrophils with multiple adhered platelets that expressed significantly more CD11b and exhibited greater oxidative activity than single neutrophils. On average, wild-type and sickle PNAs contained 1.1 and 2.6 platelets per neutrophil, respectively. Hypoxia/reoxygenation induced a further increase in PNAs in mice with SCD and additional activation of both platelets and neutrophils. The pretreatment of mice with SCD with clopidogrel or P-selectin antibody reduced the formation of PNAs and neutrophil activation and decreased lung vascular permeability. CONCLUSIONS: Our findings suggest that platelet binding activates neutrophils and contributes to a chronic inflammatory state and pulmonary dysfunction in SCD. The inhibition of platelet activation may be useful to decrease tissue injury in SCD, particularly during the early stages of vaso-occlusive crises.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SELPHumansickle cell anemia  ISOSelp (Mus musculus) RGD 
SelpRatsickle cell anemia  ISOSelp (Mus musculus) RGD 
SelpMousesickle cell anemia  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Selp  (selectin P)

Genes (Mus musculus)
Selp  (selectin, platelet)

Genes (Homo sapiens)
SELP  (selectin P)


Additional Information