Platelets enhance CD4+ lymphocyte adhesion to extracellular matrix under flow conditions: Role of platelet aggregation, integrins, and non-integrin receptors

Alexey Solpov, Boris Shenkman, Yuri Vitkovsky, Grigory Brill, Alexander Koltakov, Nahid Farzam, David Varon, Ilan Bank, Naphtali Savion

Research output: Contribution to journalArticlepeer-review

Abstract

The purpose of this study was to examine the role of platelets in CD4+ T lymphocyte adhesion to subendothelial extracellular matrix (ECM). Herpesvirus saimiri (HVS)-infected CD4+ T cells were incubated on ECM. An image analysis was used to evaluate T cell adhesion. Under static condition, T cell activation with 4-α-Phorbol 12-myristate 13-acetate (PMA) resulted in a 2.6-fold increase in cell adhesion. However, adhesion was not affected by platelets. In contrast, under flow (200s-1), platelets markedly enhanced both resting and PMA-activated T cell adhesion (33- and 48-fold), forming lymphocyte-platelet co-aggregates that contain approximately 90% of the adherent T cells. Abrogation of platelet aggregation with tirofiban inhibited formation of platelet-T cell co-aggregates under flow and reduced T cell adhesion by 74%. Separate and combined blockade of CD40L and P-selectin glycoprotein-I (PSGL-1) on PMA-activated lymphocytes reduced adhesion under flow in the presence of platelets by 28%, 33%, and 55%, respectively. Blockade of β1-integrins decreased adhesion under both static and flow conditions (by 35% and 44%, respectively), while blockade of β2-integrin reduced adhesion only under static condition (by 23%). A similar adhesion pattern was observed using CD4+ T cells isolated from normal donor peripheral blood. In conclusion, platelets support CD4+ lymphocyte adhesion to ECM under flow by formation of heterotypic platelet-lymphocyte co-aggregates involving αIIbβ 3 integrin and β1-related integrins, as well as CD40L and PSGL-1.

Original languageEnglish
Pages (from-to)815-821
Number of pages7
JournalThrombosis and Haemostasis
Volume95
Issue number5
DOIs
StatePublished - May 2006

Keywords

  • CD4+ T cells
  • CD40L
  • Integrins
  • PSGL-I
  • Platelets

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