Platelet-monocyte complex formation: effect of blocking PSGL-1 alone, and in combination with alphaIIbbeta3 and alphaMbeta2, in coronary stenting.
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.
Fernandes
Laura S
LS
Baylor College of Medicine and the Methodist DeBakey Heart Center, USA.
Conde
Ian D
ID
Wayne Smith
C
C
Kansas
Geoffrey S
GS
Snapp
Karen R
KR
Bennet
Nelson
N
Ballantyne
Christie
C
McIntire
Larry V
LV
O'Brian Smith
E
E
Klem
Jeffrey A
JA
Mathew
Shiba
S
Frangogiannis
Nikolaos
N
Turner
Nancy A
NA
Maresh
Kelley J
KJ
Kleiman
Neal S
NS
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
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019039:Platelet Glycoprotein GPIIb-IIIa Complex