title: Platelet-Derived CCL5 Regulates CXC Chemokine Formation and Neutrophil Recruitment in Acute Experimental Colitis.
abstract: Accumulating data suggest that platelets not only regulate thrombosis and haemostasis but also inflammatory processes. Platelets contain numerous potent pro-inflammatory compounds, including the chemokines CCL5 and CXCL4, although their role in acute colitis remains elusive. The aim of this study is to examine the role of platelets and platelet-derived chemokines in acute colitis. Acute colitis is induced in female Balb/c mice by administration of 5% dextran sodium sulfate (DSS) for 5 days. Animals receive a platelet-depleting, anti-CCL5, anti-CXCL4, or a control antibody prior to DSS challenge. Colonic tissue is collected for quantification of myeloperoxidase (MPO) activity, CXCL5, CXCL2, interleukin-6 (IL-6), and CCL5 levels as well as morphological analyses. Platelet depletion reduce tissue damage and clinical disease activity index in DSS-exposed animals. Platelet depletion not only reduces levels of CXCL2 and CXCL5 but also levels of CCL5 in the inflamed colon. Immunoneutralization of CCL5 but not CXCL4 reduces tissue damage, CXC chemokine expression, and neutrophil recruitment in DSS-treated animals. These findings show that platelets play a key role in acute colitis by regulating CXC chemokine generation, neutrophil infiltration, and tissue damage in the colon. Moreover, our results suggest that platelet-derived CCL5 is an important link between platelet activation and neutrophil recruitment in acute colitis.
authors.affiliation: Department of Clinical Sciences Section of Surgery, Malmö Lund University, Malmö, Sweden.|Department of Gastroenterology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Changhui
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Clinical Sciences Section of Surgery, Malmö Lund University, Malmö, Sweden.
authors.forename: Songen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Clinical Sciences Section of Surgery, Malmö Lund University, Malmö, Sweden.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Clinical Sciences Section of Surgery, Malmö Lund University, Malmö, Sweden.
authors.forename: Su
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Clinical Sciences Section of Surgery, Malmö Lund University, Malmö, Sweden.
authors.forename: Lingtao
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Clinical Sciences Section of Surgery, Malmö Lund University, Malmö, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Thorlacius
mesh_terms: D000208:Acute Disease; D000818:Animals; D001792:Blood Platelets / Q000276:immunology*; D018946:Chemokine CCL5 / Q000097:blood*; D019743:Chemokines, CXC / Q000096:biosynthesis*; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D015539:Platelet Activation; D010978:Platelet Factor 4 / Q000097:blood
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D019743:Chemokines, CXC; D010978:Platelet Factor 4; D009195:Peroxidase