Peripheral blood cultured mast cells: Phenotypic and functional outcomes of different culture protocols

Elst, Jessy; Sabato, Vito; Poorten, Marie-Line M. van der; Faber, Margaretha A.; Gasse, Athina L. Van; Puysseleyr, Leander P. De; Bridts, Chris H.; Mertens, Christel; Houdt, Michel van; Maurer, Marcus; Hagendorens, Margo M.; Ebo, Didier G.

doi:10.1016/j.jim.2021.113003

Cited by 10 publications

(20 citation statements)

References 43 publications

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“…As shown in Figure 2, PBCMCs, cultured for 4 weeks in the presence of SCF and IL-3, are characterized by CD117 and CD203c expression. 62 Besides, these PBCMCs uniformly express other membrane markers as the FcεRI, CD300a and CD32. MRGPRX2 is partially expressed, creating two distinctive subpopulations, MRGPRX2 + and MRGPRX2 − cells.…”

Section: Culture Techniquesmentioning

confidence: 97%

“…6,10,[59][60][61] CD203c (or ENPP-3), an ectonucleotide pyrophosphatase/phosphodiesterase family member, is already expressed on the cell surface of quiescent MCs and is up-regulated after stimulation. 15,59,61,62 However, the up-regulation of CD203c and CD63 is clearly different. Actually, up-regulation of CD63, unlike up-regulation of CD203c, is generally bimodal with a subpopulation of degranulating cells that express CD63 with a high intensity versus a resting subpopulation with a significant lower expression.…”

Section: Key Messagesmentioning

confidence: 98%

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Mast cell activation tests by flow cytometry: A new diagnostic asset?

Elst

Poorten

Gasse

et al. 2021

Clin Experimental Allergy

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Since the late nineties, evidence has accumulated that flow-assisted basophil activation test (BAT) might be an accessible and reliable method to explore the mechanisms governing basophil degranulation and diagnostic allowing correct prediction of the clinical outcome following exposure to the offending allergen(s) and cross-reactive structures for different IgE-dependent allergies and particular forms of autoimmune urticaria. Although the BAT offers many advantages over mediator release tests, it is left with some weaknesses that hinder a wider application. It is preferable to perform the BAT analysis within 4 h of collection, and the technique does not advance diagnosis in patients with non-responsive cells. Besides, the BAT is difficult to standardize mainly because of the difficulty to perform large batch analyses that might span over several days. This article reviews the status of flow cytometric mast cell activation test (MAT) using passively sensitized mast cells (MCs) with patients' sera or plasma (henceforth indicated as passive MAT; pMAT) using both MC lines and cultured MCs in the diagnosis of IgE-dependent allergies. In addition, this paper provides guidance for generating human MCs from peripheral blood CD34 + progenitor cells (PBCMCs) and correct interpretation of flow cytometric analyses of activated and/or degranulating cells. With the recent recognition of the mas-related G protein-coupled receptor X2 (MRGPRX2) occupation as a putative mechanism of immediate drug hypersensitivity reactions (IDHRs), we also speculate how direct activation of MCs (dMAT)-that

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Section: Culture Techniquesmentioning

confidence: 97%

Section: Key Messagesmentioning

confidence: 98%

Mast cell activation tests by flow cytometry: A new diagnostic asset?

Elst

Poorten

Gasse

et al. 2021

Clin Experimental Allergy

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“…Regulators of MRGPRX2 expression, at the transcriptional and/or post-transcription levels remain unclear. Chronic IL-6 treatment during the generation of blood-derived mast cells only modestly enhanced MRGPRX2 surface levels and function (36). Thymic stromal lymphopoetin (TSLP) was recently shown to selectively enhance MRGPRX2-mediated degranulation of skin mast cells (37).…”

Section: Elevated And/or Expanded Expression or Function Of Mrgprx2 In Mast Cellsmentioning

confidence: 99%

“…In such studies, CD34 + blood progenitor cells could be cultured into mature mast cells. Numerous methods exist, and these have been recently compared (36). A recent study has compared blood-derived mast cells from patients who had likely IgE-dependent with a possible MRGPRX2-dependent drug-induced anaphylaxis (46).…”

Section: Elevated And/or Expanded Expression or Function Of Mrgprx2 In Mast Cellsmentioning

confidence: 99%

Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target

et al. 2021

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Acute anaphylaxis to small molecule drugs is largely considered to be antibody-mediated with immunogloblin E (IgE) and mast cell activation being key. More recently, a role for drug-reactive immunoglobulin G (IgG) with neutrophil activation has also been suggested, at least in reactions to neuromuscular blocking agents (NMBAs). However, the mast cell receptor MRGPRX2 has also been highlighted as a possible triggering mechanism in acute anaphylaxis to many clinically used drugs. Significantly, MRGPRX2 activation is not dependent upon the presence of drug-recognising antibody. Given the reasonable assumption that MRGPRX2 is expressed in all individuals, the corollary of this is that in theory, anybody could respond detrimentally to triggering drugs (recently suggested to be around 20% of a drug-like compound library). But this clearly is not the case, as the incidence of acute drug-induced anaphylaxis is very low. In this mini-review we consider antibody-dependent and -independent mechanisms of mast cell activation by small molecule drugs with a focus on the MRGPRX2 pathway. Moreover, as a juxtaposition to these adverse drug actions, we consider how increased understanding of the role of MRGPRX2 in anaphylaxis is important for future drug development and can complement exploration of this receptor as a drug target in broader clinical settings.

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“…Furthermore, it was demonstrated that these cells (henceforth called PBCMCs) respond to both allergen-specific cross-linking of IgE/FcεRI complexes and occupation of the MRGPRX2 by its natural ligand substance P, a tachykinin neuropeptide 23,[27][28][29][30] .…”

Section: Introductionmentioning

confidence: 99%