PMID- 26588084 OWN - NLM STAT- MEDLINE DCOM- 20170313 LR - 20220318 IS - 1369-1635 (Electronic) IS - 0953-7104 (Linking) VI - 27 IP - 4 DP - 2016 Jun TI - Platelets attenuate production of cytokines and nitric oxide by macrophages in response to bacterial endotoxin. PG - 344-50 LID - 10.3109/09537104.2015.1103369 [doi] AB - 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-alpha (TNF)-alpha, 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-alpha, 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. FAU - Ando, Yusuke AU - Ando Y AD - a Department of Microbiology , Hoshi University School of Pharmacy and Pharmaceutical Sciences , Tokyo , Japan. FAU - Oku, Teruaki AU - Oku T AD - a Department of Microbiology , Hoshi University School of Pharmacy and Pharmaceutical Sciences , Tokyo , Japan. FAU - Tsuji, Tsutomu AU - Tsuji T AD - a Department of Microbiology , Hoshi University School of Pharmacy and Pharmaceutical Sciences , Tokyo , Japan. LA - eng PT - Journal Article DEP - 20151120 PL - England TA - Platelets JT - Platelets JID - 9208117 RN - 0 (Culture Media, Conditioned) RN - 0 (Cytokines) RN - 0 (Endotoxins) RN - 0 (Lipopolysaccharides) RN - 31C4KY9ESH (Nitric Oxide) RN - 9010-72-4 (Zymosan) RN - EC 3.4.21.5 (Thrombin) SB - IM MH - Animals MH - Blood Platelets/*metabolism MH - Cell Line MH - Culture Media, Conditioned/pharmacology MH - Cytokines/*biosynthesis MH - Endotoxins/*metabolism MH - Humans MH - Lipopolysaccharides/immunology MH - Macrophage Activation/immunology MH - Macrophages/drug effects/*immunology/*metabolism MH - Mice MH - Nitric Oxide/*biosynthesis MH - Thrombin/pharmacology MH - Zymosan/immunology OTO - NOTNLM OT - Bacterial endotoxin OT - cytokines OT - macrophage OT - nitric oxide OT - platelet EDAT- 2015/11/21 06:00 MHDA- 2017/03/14 06:00 CRDT- 2015/11/21 06:00 PHST- 2015/11/21 06:00 [entrez] PHST- 2015/11/21 06:00 [pubmed] PHST- 2017/03/14 06:00 [medline] AID - 10.3109/09537104.2015.1103369 [doi] PST - ppublish SO - Platelets. 2016 Jun;27(4):344-50. doi: 10.3109/09537104.2015.1103369. Epub 2015 Nov 20.