title: Platelet-monocyte complex formation: effect of blocking PSGL-1 alone, and in combination with alphaIIbbeta3 and alphaMbeta2, in coronary stenting.
abstract: BACKGROUND
  Binding of platelet P-selectin to P-selectin glycoprotein ligand 1 (PSGL-1) is an initial event in the interactions between platelets and monocytes. Platelet-monocyte complexes (PMCs) have been implicated in several vascular disease processes, including acute coronary syndromes (ACS) and complications after percutaneous coronary intervention (PCI). We investigated the effect of ex vivo blockade of PSGL-1, alone and in combination with blockade of the alphaMbeta(2) (Mac-1) and alpha(IIb)beta(3) (GP IIb/IIIa) integrins, on PMC formation.
  
  
  RESULTS
  Dual-label flow cytometry was used to detect PMCs in the blood of 10 volunteers and 10 patients undergoing PCI who received intravenous GP IIb/IIIa antagonists. PSGL-1 blockade, both prior to and after platelet stimulation, markedly reduced the formation of PMCs. Concomitant ex vivo blockade of the alphaMbeta(2) and alpha(IIb)beta(3) integrins did not result in further decreases of PMCs compared to PSGL-1 blockade alone. Antagonism of PSGL-1 also led to near elimination of leukocyte-platelet interactions under flowing conditions.
  
  
  CONCLUSIONS
  Blockade of PSGL-1 alone is sufficient to inhibit and reverse the formation of PMCs following platelet stimulation. Concurrent antagonism of PSGL-1 and the alpha(IIb)beta(3) and alphaMbeta(2) integrins was not more effective than inhibition of PSGL-1 alone. These results suggest that platelet-monocyte complex formation is mostly dependent on PSGL-1.
authors.affiliation: Baylor College of Medicine and the Methodist DeBakey Heart Center, USA.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Fernandes
authors.forename: Ian D
authors.initials: ID
authors.lastname: Conde
authors.forename: C
authors.initials: C
authors.lastname: Wayne Smith
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Kansas
authors.forename: Karen R
authors.initials: KR
authors.lastname: Snapp
authors.forename: Nelson
authors.initials: N
authors.lastname: Bennet
authors.forename: Christie
authors.initials: C
authors.lastname: Ballantyne
authors.forename: Larry V
authors.initials: LV
authors.lastname: McIntire
authors.forename: E
authors.initials: E
authors.lastname: O'Brian Smith
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Klem
authors.forename: Shiba
authors.initials: S
authors.lastname: Mathew
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Frangogiannis
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Turner
authors.forename: Kelley J
authors.initials: KJ
authors.lastname: Maresh
authors.forename: Neal S
authors.initials: NS
authors.lastname: Kleiman
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D007962:Leukocytes / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019039:Platelet Glycoprotein GPIIb-IIIa Complex