Platelets enhance CD4+ lymphocyte adhesion to extracellular matrix under flow conditions: role of platelet aggregation, integrins, and non-integrin receptors.
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-alpha-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-1 (PSGL-1) on PMA-activated lymphocytes reduced adhesion under flow in the presence of platelets by 28%, 33%, and 55%, respectively. Blockade of beta1-integrins decreased adhesion under both static and flow conditions (by 35% and 44%, respectively), while blockade of beta2-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 coaggregates involving alphaIIbbeta3 integrin and beta1-related integrins, as well as CD40L and PSGL-1.
Solpov
Alexey
A
Department of Physiology, Chita Medical Academy, Chita, Russia.
Shenkman
Boris
B
Vitkovsky
Yuri
Y
Brill
Grigory
G
Koltakov
Alexander
A
Farzam
Nahid
N
Varon
David
D
Bank
Ilan
I
Savion
Naphtali
N