RGD Reference Report - The CXCR1/2 ligand NAP-2 promotes directed intravascular leukocyte migration through platelet thrombi. - Rat Genome Database

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The CXCR1/2 ligand NAP-2 promotes directed intravascular leukocyte migration through platelet thrombi.

Authors: Ghasemzadeh, Mehran  Kaplan, Zane S  Alwis, Imala  Schoenwaelder, Simone M  Ashworth, Katrina J  Westein, Erik  Hosseini, Ehteramolsadat  Salem, Hatem H  Slattery, Robyn  McColl, Shaun R  Hickey, Michael J  Ruggeri, Zaverio M  Yuan, Yuping  Jackson, Shaun P 
Citation: Ghasemzadeh M, etal., Blood. 2013 May 30;121(22):4555-66. doi: 10.1182/blood-2012-09-459636. Epub 2013 Apr 2.
RGD ID: 401794958
Pubmed: PMID:23550035   (View Abstract at PubMed)
PMCID: PMC3953078   (View Article at PubMed Central)
DOI: DOI:10.1182/blood-2012-09-459636   (Journal Full-text)

Thrombosis promotes leukocyte infiltration into inflamed tissues, leading to organ injury in a broad range of diseases; however, the mechanisms by which thrombi guide leukocytes to sites of vascular injury remain ill-defined. Using mouse models of endothelial injury (traumatic or ischemia reperfusion), we demonstrate a distinct process of leukocyte recruitment, termed "directed intravascular migration," specifically mediated by platelet thrombi. Single adherent platelets and platelet aggregates stimulated leukocyte shape change at sites of endothelial injury; however, only thrombi were capable of inducing directed intravascular leukocyte migration. Leukocyte recruitment and migration induced by platelet thrombi occurred most prominently in veins but could also occur in arteries following ischemia-reperfusion injury. In vitro studies demonstrated a major role for platelet-derived NAP-2 (CXCL-7) and its CXCR1/2 receptor in regulating leukocyte polarization and motility. In vivo studies demonstrated the presence of an NAP-2 chemotactic gradient within the thrombus body. Pharmacologic blockade of CXCR1/2 as well as genetic deletion of NAP-2 markedly reduced leukocyte shape change and intrathrombus migration. These studies define a distinct process of leukocyte migration that is initiated by homotypic adhesive interactions between platelets, leading to the development of an NAP-2 chemotactic gradient within the thrombus body that guides leukocytes to sites of vascular injury.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PPBPHumanVenous Thrombosis amelioratesISOPpbp (Mus musculus) RGD 
PpbpRatVenous Thrombosis amelioratesISOPpbp (Mus musculus) RGD 
PpbpMouseVenous Thrombosis amelioratesIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppbp  (pro-platelet basic protein)

Genes (Mus musculus)
Ppbp  (pro-platelet basic protein)

Genes (Homo sapiens)
PPBP  (pro-platelet basic protein)


Additional Information