Role of platelets for tissue remodelling - modulation of angiogenesis, inflammation and apoptosis
Final Report Abstract
Platelet activation and thrombus formation plays a pivotal role in hemostasis and arterial thrombosis. Recent studies show that platelets can mediate tissue remodeling processes. Subproject TP7 characterized the role of platelets in tissue remodeling by studying angiogenesis, inflammation, and apoptosis. The first funding period showed that adhesion receptors as well as secreted mediators from platelets can modulate angiogenesis. Furthermore, the results from the first funding period pointed out that platelets may contribute to apoptosis, a further tissue remodeling process, via membrane-bound Fas- L. Platelet receptors of innate immunity like the anaphylatoxin receptor C5a receptor 1 (C5aR1) affect angiogenesis as well as platelet function. These receptors most likely modulate angiogenesis, apoptosis, and inflammation, three important mechanisms for tissue remodeling. Complement anaphylatoxins as well as opsonized complement components like C1q und C3 play a key role in wound healing. Recent studies show an interaction between platelets and activated C3 mediated by platelet receptor GPIb. A possible mechanism how platelets interact with damaged tissue could be the binding of apoptotic cells to complement. Furthermore, different interactions between complement system and platelet activation are discussed and need further studies. The objective of TP 7 was to define the importance of platelets in the modulation of the above-mentioned processes in various in vivo settings (e.g. hindlimb ischemia or myocardial infarction) and the mechanistic insights of mediating platelet effectors like the abovementioned apoptosis- and inflammation-mediated receptors (C5aR1) and paracrine mediators (antiangiogenic factor platelet factor 4 (PF-4, CXCL4)).
Publications
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Interruption of classic CD40L-CD40 signalling but not of the novel CD40L-Mac-1 interaction limits arterial neointima formation in mice. Thromb Haemost. 2014 Aug;112(2):379-89
Willecke F, Tiwari S, Rupprecht B, Wolf D, Hergeth S, Hoppe N, Dufner B, Schulte L, Anto Michel N, Bukosza N, Marchini T, Jäckel M, Stachon P, Hilgendorf I, Zeschky K, Schleicher R, Langer HF, von Zur Muhlen C, Bode C, Peter K, Zirlik A
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Platelets induce apoptosis via membranebound FasL, Blood. 126 (2015) 1483–1493
R.I. Schleicher, F. Reichenbach, P. Kraft, A. Kumar, M. Lescan, F. Todt, K. Göbel, I. Hilgendorf, T. Geisler, A. Bauer, M. Olbrich, M. Schaller, S. Wesselborg, L. O’Reilly, S.G. Meuth, K. Schulze- Osthoff, M. Gawaz, X. Li, C. Kleinschnitz, F. Edlich, H.F. Langer, K. Gobel, I. Hilgendorf, T. Geisler, A. Bauer, M. Olbrich, M. Schaller, S. Wesselborg, L. OReilly, S.G. Meuth, K. Schulze-Osthoff, M. Gawaz, X. Li, C. Kleinschnitz, F. Edlich, H.F. Langer
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Platelet derived Fas-L contributes to apoptosis in stroke, Thromb. Haemost. 116 (2016) 998–1000
P. Kraft, R. Schleicher, M. Olbrich, M.K. Schuhmann, K.D. Blanz, F. Emschermann, S. Ebenhoech, C. Starz, I. Hilgendorf, S.G. Meuth, F. Edlich, C. Kleinschnitz, H.F. Langer
