Flow Cytometry-Based Characterization of Mast Cells in Human Atherosclerosis.

Autor: Kritikou E; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands. e.kritikou@lacdr.leidenuniv.nl., Depuydt MAC; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands. m.a.c.depuydt@lacdr.leidenuniv.nl., de Vries MR; Department of Surgery, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands. m.r.de_vries@lumc.nl.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands. m.r.de_vries@lumc.nl., Mulder KE; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands. kevin.evan@hotmail.com., Govaert AM; Department of Surgery, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands. a.m.govaert@lumc.nl.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands. a.m.govaert@lumc.nl., Smit MD; Department of Surgery, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands. m.d.smit@lumc.nl.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands. m.d.smit@lumc.nl., van Duijn J; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands. a.c.foks@lacdr.leidenuniv.nl., Foks AC; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands. a.c.foks@lacdr.leidenuniv.nl., Wezel A; Department of Surgery, HMC Westeinde, 2512 VA The Hague, The Netherlands. a.wezel@haaglandenmc.nl., Smeets HJ; Department of Surgery, HMC Westeinde, 2512 VA The Hague, The Netherlands. h.smeets@haaglandenmc.nl., Slütter B; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands. b.a.slutter@lacdr.leidenuniv.nl., Quax PHA; Department of Surgery, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands. p.h.a.quax@lumc.nl.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands. p.h.a.quax@lumc.nl., Kuiper J; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands. j.kuiper@lacdr.leidenuniv.nl., Bot I; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands. i.bot@lacdr.leidenuniv.nl.
Jazyk: angličtina
Zdroj: Cells [Cells] 2019 Apr 09; Vol. 8 (4). Date of Electronic Publication: 2019 Apr 09.
DOI: 10.3390/cells8040334
Abstrakt: The presence of mast cells in human atherosclerotic plaques has been associated with adverse cardiovascular events. Mast cell activation, through the classical antigen sensitized-IgE binding to their characteristic Fcε-receptor, causes the release of their cytoplasmic granules. These granules are filled with neutral proteases such as tryptase, but also with histamine and pro-inflammatory mediators. Mast cells accumulate in high numbers within human atherosclerotic tissue, particularly in the shoulder region of the plaque. These findings are largely based on immunohistochemistry, which does not allow for the extensive characterization of these mast cells and of the local mast cell activation mechanisms. In this study, we thus aimed to develop a new flow-cytometry based methodology in order to analyze mast cells in human atherosclerosis. We enzymatically digested 22 human plaque samples, collected after femoral and carotid endarterectomy surgery, after which we prepared a single cell suspension for flow cytometry. We were able to identify a specific mast cell population expressing both CD117 and the FcεR, and observed that most of the intraplaque mast cells were activated based on their CD63 protein expression. Furthermore, most of the activated mast cells had IgE fragments bound on their surface, while another fraction showed IgE-independent activation. In conclusion, we are able to distinguish a clear mast cell population in human atherosclerotic plaques, and this study establishes a strong relationship between the presence of IgE and the activation of mast cells in advanced atherosclerosis. Our data pave the way for potential therapeutic intervention through targeting IgE-mediated actions in human atherosclerosis.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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