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Differential and additive effects of platelet‐derived chemokines on monocyte arrest on inflamed endothelium under flow conditions
Author(s) -
Baltus Thomas,
Hundelshausen Philipp,
Mause Sebastian F.,
Buhre Wolfgang,
Rossaint Rolf,
Weber Christian
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0305141
Subject(s) - chemokine , monocyte , cx3cl1 , platelet factor 4 , platelet , immunology , ccl5 , chemistry , microbiology and biotechnology , biology , chemokine receptor , inflammation , t cell , immune system , il 2 receptor
Platelet‐derived chemokines, such as regulated on activation, normal T expressed and secreted (RANTES; CC chemokine ligand 5), platelet factor 4 [PF4; CXC chemokine ligand 4 (CXCL4)], and epithelial neutrophil‐activating protein 78 (ENA‐78; CXCL5), or precursors, such as β‐thromboglobulin, which can be processed to neutrophil‐activating protein‐2 (NAP‐2; CXCL7), may play an important role in monocyte recruitment during atherogenesis. Platelets can deposit chemokines on inflamed endothelium; however, little is known about differential or additive effects of platelet chemokines on monocyte arrest. Here, we demonstrate that preincubation of activated human microvascular endothelial cells (HMVECs) with RANTES, PF4, or NAP‐2 but not ENA‐78 dose‐dependently increased surface immobilization and subsequent monocyte arrest in flow. RANTES was the most potent and efficient arrest chemokine. Pretreatment of HMVECs with β‐thromboglobulin enhanced monocyte arrest in the presence of cathepsin G generating NAP‐2. Combined pretreatment of HMVECs with RANTES and PF4 at suboptimal concentrations synergistically increased arrest, and preincubation with chondroitinase ABC abrogated RANTES‐ and PF4‐induced monocyte arrest. This was associated with reduced expression of chondroitin sulfate, RANTES, and PF4 on the HMVEC surface. Perfusion of HMVECs with platelets known to deposit RANTES and PF4 on the endothelial surface enhanced monocyte arrest, which was inhibited by Met‐RANTES, chondroitinase, or a blocking antibody to PF4 but not to ENA‐78. The relevance of platelet‐derived chemokines was confirmed in adhesion assays with activated whole blood, where Met‐RANTES and to a lesser extent, antibodies to PF4 and NAP‐2 inhibited arrest of CD14‐positive monocytes. Thus, multiple platelet‐derived chemokines and processable precursors, which can be presented by specific endothelial proteoglycans, may contribute and cooperate differentially to induce monocyte recruitment.