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Platelet membranes induce airway smooth muscle cellproliferation
Linköping University, Department of Medicine and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
Department of Biomedicine, School of Health and Medical Sciences, Örebro University, Sweden.
Linköping University, Department of Medicine and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
2011 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 22, no 1, 45-55 p.Article in journal (Refereed) Published
Abstract [en]

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 localised 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 were 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 GPASMC (129.9 ± 3.0 %) and H-ASMC (144.8 ± 12.2). However, neither supernatants obtained from lysed nor filtrate from thrombin stimulated platelets did induce ASMC proliferation to the same extent as the membrane preparation. We have previously shown the platelet-induced proliferation is dependent on the 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.

Place, publisher, year, edition, pages
Informa , 2011. Vol. 22, no 1, 45-55 p.
Keyword [en]
platelets; platelet membranes; airway smooth muscle cell; 5-lipoxygenase; reactive oxygen species; airway remodeling
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-61615DOI: 10.3109/09537104.2010.515696ISI: 000286937800006OAI: oai:DiVA.org:liu-61615DiVA: diva2:370611
Note
Original Publication: Ann-Charlotte B. Svensson Holm, Torbjörn Bengtsson, Magnus Grenegård and Eva G. Lindström, Platelet membranes induce airway smooth muscle cellproliferation, 2011, Platelets, (22), 1, 45-55. http://dx.doi.org/10.3109/09537104.2010.515696 Copyright: Informa Healthcare http://informahealthcare.com/ Available from: 2010-11-17 Created: 2010-11-17 Last updated: 2017-12-12
In thesis
1. Platelets and airway remodeling: Mechanisms involved in platelet-induced fibroblast and airway smooth muscle cell proliferation in vitro
Open this publication in new window or tab >>Platelets and airway remodeling: Mechanisms involved in platelet-induced fibroblast and airway smooth muscle cell proliferation in vitro
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Airway remodeling is a contributing cause to the pathological structural changes, such as increased cell proliferation, observed in asthma. Platelets have been found in autopsy lungmaterial obtained from asthmatic patients and are well known to induce proliferation in vitro of a variety of cells. However, the role of platelets in airway remodeling is far from understood. This thesis aims to clarify the involvement of platelets in fibroblast and airway smooth muscle cell (ASMC) proliferation in vitro and to elucidate the importance of HA, FAK, eicosanoid and ROS dependent signaling. The results demonstrate that platelets induce ASMC proliferation through NADPH-oxidase and 5-LOX dependent mechanisms. In addition, platelets also induce a 5-LOX dependent fibroblast proliferation. Furthermore, morphological analysis demonstrates that platelets bind to the extracellular matrix component HA through its receptor CD44 and thereby induce a FAK dependent ASMC proliferation. Taken together, the results obtained in this thesis suggest that platelet/HA interaction mediated through CD44 is of importance for platelets ability to induce cell proliferation. Moreover, the results propose that platelet-induced fibroblast proliferation is 5-LOX dependent and that platelets induce a HA, CD44, FAK, 5-LOX, and ROSdependent ASMC proliferation. This action of platelets represents a potential important and novel mechanism that may have an impact on the remodeling process and in the development of new pharmacological strategies in the treatment of inflammatory respiratory disease such as asthma.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 80 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1203
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-61623 (URN)978-91-7393-324-7 (ISBN)
Public defence
2010-12-03, Berzeliussalen, Universitetssjukhuset, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2010-11-17 Created: 2010-11-17 Last updated: 2012-01-30Bibliographically approved

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