Platelet-monocyte complex formation

Effect of blocking PSGL-1 alone, and in combination with αiIbβ3 and αmβ2, in coronary stenting

Laura S. Fernandes, Ian D. Conde, C. Wayne Smith, Geoffrey S. Kansas, Karen R. Snapp, Nelson Bennet, Christie Ballantyne, Larry V. McIntire, E. O Brian Smith, Jeffrey A. Klem, Shiba Mathew, Nikolaos G. Frangogiannis, Nancy A. Turner, Kelley J. Maresh, Neal S. Kleiman

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 αMβ2 (Mac-1) and α IIbβ3 (GP IIb/IIIa) integrins, on PMC formation. Methods and 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 αMβ2 and αIIbβ 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. Conclusion: 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 αIIbβ3 and αMβ2 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.

Original languageEnglish (US)
Pages (from-to)171-177
Number of pages7
JournalThrombosis Research
Volume111
Issue number3
DOIs
StatePublished - 2003
Externally publishedYes

Fingerprint

Monocytes
Blood Platelets
Integrins
Platelet Membrane Glycoprotein IIb
Percutaneous Coronary Intervention
P-selectin ligand protein
P-Selectin
Acute Coronary Syndrome
Vascular Diseases
Volunteers
Flow Cytometry
Leukocytes

Keywords

  • Monocyte
  • P-selectin
  • Platelet
  • PSGL-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Hematology

Cite this

Fernandes, L. S., Conde, I. D., Smith, C. W., Kansas, G. S., Snapp, K. R., Bennet, N., ... Kleiman, N. S. (2003). Platelet-monocyte complex formation: Effect of blocking PSGL-1 alone, and in combination with αiIbβ3 and αmβ2, in coronary stenting. Thrombosis Research, 111(3), 171-177. https://doi.org/10.1016/j.thromres.2003.08.017

Platelet-monocyte complex formation : Effect of blocking PSGL-1 alone, and in combination with αiIbβ3 and αmβ2, in coronary stenting. / Fernandes, Laura S.; Conde, Ian D.; Smith, C. Wayne; Kansas, Geoffrey S.; Snapp, Karen R.; Bennet, Nelson; Ballantyne, Christie; McIntire, Larry V.; Smith, E. O Brian; Klem, Jeffrey A.; Mathew, Shiba; Frangogiannis, Nikolaos G.; Turner, Nancy A.; Maresh, Kelley J.; Kleiman, Neal S.

In: Thrombosis Research, Vol. 111, No. 3, 2003, p. 171-177.

Research output: Contribution to journalArticle

Fernandes, LS, Conde, ID, Smith, CW, Kansas, GS, Snapp, KR, Bennet, N, Ballantyne, C, McIntire, LV, Smith, EOB, Klem, JA, Mathew, S, Frangogiannis, NG, Turner, NA, Maresh, KJ & Kleiman, NS 2003, 'Platelet-monocyte complex formation: Effect of blocking PSGL-1 alone, and in combination with αiIbβ3 and αmβ2, in coronary stenting', Thrombosis Research, vol. 111, no. 3, pp. 171-177. https://doi.org/10.1016/j.thromres.2003.08.017
Fernandes, Laura S. ; Conde, Ian D. ; Smith, C. Wayne ; Kansas, Geoffrey S. ; Snapp, Karen R. ; Bennet, Nelson ; Ballantyne, Christie ; McIntire, Larry V. ; Smith, E. O Brian ; Klem, Jeffrey A. ; Mathew, Shiba ; Frangogiannis, Nikolaos G. ; Turner, Nancy A. ; Maresh, Kelley J. ; Kleiman, Neal S. / Platelet-monocyte complex formation : Effect of blocking PSGL-1 alone, and in combination with αiIbβ3 and αmβ2, in coronary stenting. In: Thrombosis Research. 2003 ; Vol. 111, No. 3. pp. 171-177.
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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 αMβ2 (Mac-1) and α IIbβ3 (GP IIb/IIIa) integrins, on PMC formation. Methods and 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 αMβ2 and αIIbβ 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. Conclusion: 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 αIIbβ3 and αMβ2 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.",
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T1 - Platelet-monocyte complex formation

T2 - Effect of blocking PSGL-1 alone, and in combination with αiIbβ3 and αmβ2, in coronary stenting

AU - Fernandes, Laura S.

AU - Conde, Ian D.

AU - Smith, C. Wayne

AU - Kansas, Geoffrey S.

AU - Snapp, Karen R.

AU - Bennet, Nelson

AU - Ballantyne, Christie

AU - McIntire, Larry V.

AU - Smith, E. O Brian

AU - Klem, Jeffrey A.

AU - Mathew, Shiba

AU - Frangogiannis, Nikolaos G.

AU - Turner, Nancy A.

AU - Maresh, Kelley J.

AU - Kleiman, Neal S.

PY - 2003

Y1 - 2003

N2 - 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 αMβ2 (Mac-1) and α IIbβ3 (GP IIb/IIIa) integrins, on PMC formation. Methods and 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 αMβ2 and αIIbβ 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. Conclusion: 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 αIIbβ3 and αMβ2 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.

AB - 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 αMβ2 (Mac-1) and α IIbβ3 (GP IIb/IIIa) integrins, on PMC formation. Methods and 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 αMβ2 and αIIbβ 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. Conclusion: 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 αIIbβ3 and αMβ2 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.

KW - Monocyte

KW - P-selectin

KW - Platelet

KW - PSGL-1

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DO - 10.1016/j.thromres.2003.08.017

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EP - 177

JO - Thrombosis Research

JF - Thrombosis Research

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