title: Platelets attenuate production of cytokines and nitric oxide by macrophages in response to bacterial endotoxin.
abstract: Considerable evidence has been accumulated concerning the roles of platelets in immune responses. In the present study, we examined the functional modulation of macrophages by platelets. When mouse bone marrow-derived macrophages (BMDMs) were co-cultured with platelets, BMDMs produced lower levels of nitric oxide (NO), tumor necrosis factor-α (TNF)-α, and interleukin (IL)-6 in response to a bacterial endotoxin (LPS) and zymosan. The attenuation in the macrophage susceptibility to LPS appeared to be mediated by soluble factors secreted from platelets. The mRNA levels of NOS2 (iNOS), TNF-α, and IL-6 in LPS-stimulated BMDMs that had been cultured with a conditioned medium of platelets were also decreased as analyzed by RT-qPCR. The ability of the platelet-conditioned medium to suppress macrophage NO production was recovered in a high-molecular-weight fraction (>670 kDa) after gel-filtration chromatography on a Superose 6 column. These results suggest that platelets control the susceptibility of macrophages to prevent excessive responses to LPS and provide mechanistic insight into a previous report that experimental thrombocytopenia aggravated organ failure in LPS-induced endotoxemia.
authors.affiliation: a Department of Microbiology , Hoshi University School of Pharmacy and Pharmaceutical Sciences , Tokyo , Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ando
authors.affiliation: a Department of Microbiology , Hoshi University School of Pharmacy and Pharmaceutical Sciences , Tokyo , Japan.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Oku
authors.affiliation: a Department of Microbiology , Hoshi University School of Pharmacy and Pharmaceutical Sciences , Tokyo , Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D004731:Endotoxins / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D013917:Thrombin / Q000494:pharmacology; D015054:Zymosan / Q000276:immunology
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D015054:Zymosan; D013917:Thrombin
keywords: Bacterial endotoxin; cytokines; macrophage; nitric oxide; platelet