PMID- 27714784 OWN - NLM STAT- MEDLINE DCOM- 20170606 LR - 20181202 IS - 1365-2362 (Electronic) IS - 0014-2972 (Linking) VI - 47 IP - 2 DP - 2017 Feb TI - Platelets Toll-like receptor-4 in Crohns disease. PG - 109-116 LID - 10.1111/eci.12686 [doi] AB - BACKGROUND: Platelets are activated in Crohn's disease (CD) and interplay with leukocytes. Engagement of Toll-like receptor-4 (TLR-4), which is expressed in human platelets, may be involved in crosstalks between platelets and leukocytes leading to their mutual activation for host defense. MATERIALS AND METHODS: Human neutrophil peptides (HNPs), lipoprotein binding peptides, and sCD14 were determined by enzyme-linked immunosorbent assays in 42 patients with active CD, in 43 patients with CD in remission, and in 30 healthy individuals. Neutrophil-platelet aggregates and binding of the TLR-4 monoclonal antibody to platelets were determined by flow cytometry. RESULTS: Levels of HNPs were higher in patients with CD than in controls (P = 0.0003 vs. active CD and P = 0.01 vs. CD in remission). Likewise, neutrophils with adhering platelets were higher in patients with active CD than in controls (P = 0.004). Binding of the TLR-4 antibody in patients with active CD was similar to that in controls, while patients in remission had significantly higher binding capacities (P = 0.59 and P = 0.003). Incubation of plasma from patients with active disease or patients in remission with platelets from healthy controls confirmed lower binding of the TLR-4 antibody in the presence of plasma from active diseased patients compared to controls (P = 0.039), possibly due to high levels of lipopolysaccharides, as suggested by high levels of sCD14 and lipoprotein binding protein. CONCLUSION: Our study indicates involvement of platelet TLR-4 in enhancing the secretion of antimicrobial peptides from neutrophils. While platelet aggregation can be due to a variety of mechanisms in inflammatory disease, the mutual activation of platelets and neutrophils may augment host defense. CI - (c) 2016 Stichting European Society for Clinical Investigation Journal Foundation. FAU - Schmid, Werner AU - Schmid W AD - Division of Cardiothoracic and Vascular Anesthesia and Intensive Care, Department of Anesthesiology, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria. FAU - Novacek, Gottfried AU - Novacek G AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. FAU - Vogelsang, Harald AU - Vogelsang H AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. FAU - Papay, Pavol AU - Papay P AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. FAU - Primas, Christian AU - Primas C AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. FAU - Eser, Alexander AU - Eser A AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. FAU - Panzer, Simon AU - Panzer S AD - Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria. LA - eng PT - Journal Article DEP - 20161229 PL - England TA - Eur J Clin Invest JT - European journal of clinical investigation JID - 0245331 RN - 0 (Acute-Phase Proteins) RN - 0 (Carrier Proteins) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Membrane Glycoproteins) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (alpha-Defensins) RN - 0 (lipopolysaccharide-binding protein) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Acute-Phase Proteins/metabolism MH - Adult MH - Blood Platelets/*metabolism MH - C-Reactive Protein/metabolism MH - Carrier Proteins/metabolism MH - Case-Control Studies MH - Cell Communication/physiology MH - Crohn Disease/*metabolism MH - Female MH - Flow Cytometry MH - Humans MH - Lipopolysaccharide Receptors/metabolism MH - Male MH - Membrane Glycoproteins/metabolism MH - Neutrophil Activation/physiology MH - Neutrophils/metabolism MH - Platelet Activation/physiology MH - Platelet Aggregation/physiology MH - Toll-Like Receptor 4/*physiology MH - alpha-Defensins/*metabolism OTO - NOTNLM OT - Crohn's disease OT - Toll-like receptor-4 OT - human neutrophil alpha-defensins EDAT- 2016/10/08 06:00 MHDA- 2017/06/07 06:00 CRDT- 2016/10/08 06:00 PHST- 2016/04/10 00:00 [received] PHST- 2016/10/04 00:00 [accepted] PHST- 2016/10/08 06:00 [pubmed] PHST- 2017/06/07 06:00 [medline] PHST- 2016/10/08 06:00 [entrez] AID - 10.1111/eci.12686 [doi] PST - ppublish SO - Eur J Clin Invest. 2017 Feb;47(2):109-116. doi: 10.1111/eci.12686. Epub 2016 Dec 29.