title: Platelet membranes induce airway smooth muscle cell proliferation.
abstract: The role of platelets in airway disease is poorly understood although they have been suggested to influence on proliferation of airway smooth muscle cells (ASMC). Platelets have been found localized in the airways in autopsy material from asthmatic patients and have been implicated in airway remodeling. The aim of the present study was to investigate the effects of various platelet fractions on proliferation of ASMC obtained from guinea pigs (GP-ASMC) and humans (H-ASMC). Proliferation of ASMC was measured by the MTS assay and the results confirmed by measurements of the DNA content. A key observation was that the platelet membrane preparations induced a significant increase in the proliferation of both GP-ASMC (129.9 ± 3.0 %) and H-ASMC (144.8 ± 12.2). However, neither supernatants from lysed or filtrated thrombin stimulated platelets induced ASMC proliferation to the same extent as the membrane preparation. We have previously shown that platelet-induced proliferation is dependent on 5-lipoxygenase (5-LOX) and reactive oxygen species (ROS) pathways. In the present work we established that platelet membrane-induced ASMC proliferation was reduced in the presence of the NADPH oxidase inhibitor DPI and the 5-LOX inhibitor AA-861. In conclusion, our results showed that platelet membranes significantly induced ASMC proliferation, demonstrating that the mitogenic effect of platelets and platelet membranes on ASMC is mainly due to membrane-associated factors. The effects of platelet membranes were evident on both GP-ASMC and H-ASMC and involved 5-LOX and ROS. These new findings are of importance in understanding the mechanisms contributing to airway remodeling and may contribute to the development of new pharmacological tools in the treatment of inflammatory airway diseases.
authors.affiliation: Division of Drug Research/Pharmacology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden. ann-charlotte.svensson@liu.se
authors.forename: Ann-Charlotte B
authors.initials: AC
authors.lastname: Svensson Holm
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Bengtsson
authors.forename: Magnus
authors.initials: M
authors.lastname: Grenegård
authors.forename: Eva G
authors.initials: EG
authors.lastname: Lindström
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016227:Benzoquinones / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D006168:Guinea Pigs; D006801:Humans; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction
chemical_list: D016227:Benzoquinones; D009861:Onium Compounds; D017382:Reactive Oxygen Species; C007517:diphenyleneiodonium; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D001094:Arachidonate 5-Lipoxygenase; D019255:NADPH Oxidases