Platelet-Monocyte Complexes Support Monocyte Adhesion to Endothelium by Enhancing Secondary Tethering and Cluster Formation

Abstract

Objective-Adhesion of monocytes to endothelium can be supported by monocyte-monocyte interactions resulting in the formation of cell aggregates at the vessel wall (clusters). Since platelets that are bound to the injured vessel wall support monocyte adhesion and platelet activation in the circulation leads to formation of platelet-monocyte complexes (PMCs), we examined whether adhesion of PMCs to the vessel wall enhances monocyte clustering. Methods and Results-The effect of PMC formation in monocyte adhesion and clustering on human umbilical vein endothelial cells (HUVECs) was studied in vitro with a perfusion system. In the presence of 10% to 20% PMCs, monocyte adhesion and cluster formation to stimulated HUVECs increased 2-fold above levels obtained with pure monocytes. While the observed effects increased with higher PMC levels, blocking-monoclonal antibodies directed against platelet-associated P-selectin or monocyte P-selectin glycoprotein ligand-1 (PSGL-1) reversed adhesion and clustering to control values. In the presence of PMCs, blocking L-selectin decreased adhesion by 25%. When PMCs were present, clustering was only supported by L-selectin at higher shear. These data indicate that monocyte adhesion to the vessel wall is enhanced by PMC-mediated monocyte secondary tethering. These interactions are mainly mediated by P-selectin and PSGL-1. Conclusion-PMCs

Protection against Renal Ischemia Reperfusion Injury by CD44 Disruption

“…Perfusion experiments were performed as described previously (25). In short, 1 million neutrophils were perfused through a HUVEC monolayer-containing chamber.…”

Platelet CD40L mediates thrombotic and inflammatory processes in atherosclerosis

“…[18][19][20][21][22][23][24] Moreover, activated platelets can indirectly support leukocyte recruitment via formation of platelet-leukocyte aggregates (PLAs). 25 Through P-selectin, platelets bind to the P-selectin glycoprotein ligand on leukocytes, and the multicellular conjugates produce chemokines, such as CCL2 and CCL5, and cytokines, such as interleukin-1␤ (IL-1␤), to further activate leukocytes. [23][24][25][26][27][28] In vitro observations have indicated that these conjugates tether and roll on endothelial cells with a higher avidity than nonconjugated leukocytes, thereby enhancing endothelial activation.…”

“…25 Through P-selectin, platelets bind to the P-selectin glycoprotein ligand on leukocytes, and the multicellular conjugates produce chemokines, such as CCL2 and CCL5, and cytokines, such as interleukin-1␤ (IL-1␤), to further activate leukocytes. [23][24][25][26][27][28] In vitro observations have indicated that these conjugates tether and roll on endothelial cells with a higher avidity than nonconjugated leukocytes, thereby enhancing endothelial activation. [26][27][28] In addition, PLAs have been observed in prethrombotic or prothrombotic clinical conditions, and may provide a suitable predictor of acute myocardial infarction.…”

P-Selectin Expression, but not GPIIb/IIIa Activation, is Enhanced in the Inflammatory Stage of Takayasu's Arteritis

“…It mediates the adhesion of activated platelets to neutrophils and monocytes via a specific interaction with P-selectin glycoprotein-1 5,23,24 and may trigger multiple intracellular events within leukocytes to promote vascular inflammation and facilitate atherosclerosis and thrombosis. [24][25][26][27] Clinically, an increased expression of platelet P-selectin has been shown in patients with atherothrombotic diseases, including those in the acute phase of ischemic stroke 28 and with acute coronary syndrome. 29,30 However, determination of platelet P-selectin and studies of platelet-monocyte interaction have not been performed in patients with TA.…”