Abstract
BackgroundImmunohistochemical analysis of granule-associated proteases has revealed that human lung mast cells constitute a heterogeneous population of cells, with distinct subpopulations identified. However, a systematic and comprehensive analysis of cell-surface markers to study human lung mast cell heterogeneity has yet to be performed.MethodsHuman lung mast cells were obtained from lung lobectomies, and the expression of 332 cell-surface markers was analyzed using flow cytometry and the LEGENDScreen™ kit. Markers that exhibited high variance were selected for additional analyses to reveal whether they were correlated and whether discrete mast cell subpopulations were discernable.ResultsWe identified the expression of 102 surface markers on human lung mast cells, 23 previously not described on mast cells, of which several showed high continuous variation in their expression. Six of these markers were correlated: SUSD2, CD49a, CD326, CD34, CD66 and HLA-DR. The expression of these markers was also correlated with the size and granularity of mast cells. However, no marker produced an expression profile consistent with a bi- or multimodal distribution.ConclusionsLEGENDScreen analysis identified more than 100 cell-surface markers on mast cells, including 23 that, to the best of our knowledge, have not been previously described on human mast cells. The comprehensive expression profiling of the 332 surface markers did not identify distinct mast cell subpopulations. Instead, we demonstrate the continuous nature of human lung mast cell heterogeneity.
Highlights
Heterogeneity among mast cells has been known for a long time and was first attributed to differential expression of proteoglycans in rodent mast cells, which gave them distinct staining patterns [1]
The classic division into distinct human mast cell subpopulations is based on the presence or absence of granule-associated antigens, i.e., the proteases tryptase, chymase and CPA3
The Human lung mast cells (HLMCs) population showed a high variation of chymase and CPA3 expression between individual cells and the degree of CPA3 and chymase double positive cells varied considerably from donor to donor (Figure 1C)
Summary
Heterogeneity among mast cells has been known for a long time and was first attributed to differential expression of proteoglycans in rodent mast cells, which gave them distinct staining patterns [1]. This led to the division of rodent mast cells into connective tissue mast cells and mucosal mast cells. The heterogeneity among HLMCs goes beyond size and protease expression, as demonstrated by the differential expression of certain mast cell-related markers (FceRI, IL-9R, 5-LO, LTC4S, etc.) among the MCT and MCTC populations in different lung compartments [12]. A systematic and comprehensive analysis of cell-surface markers to study human lung mast cell heterogeneity has yet to be performed
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