Immunoprofiling Reveals Novel Mast Cell Receptors and the Continuous Nature of Human Lung Mast Cell Heterogeneity

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.

Immunoprofiling reveals novel mast cell receptors and the continuous nature of human lung mast cell heterogeneity

Background: Immunohistochemical 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. Methods: Human 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. Results: We identified the expression of 102 surface markers on human lung mast cells. Several markers showed high continuous variation in expression within the mast cell population. 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. Conclusions: LEGENDScreen 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. Several of the newly described markers are known to be involved in sensing the microenvironment, and their identification can shed new light on mast cell functions. The exhaustive expression profiling of the 332 surface markers failed to detect distinct mast cell subpopulations. Instead, we demonstrate the continuous nature of human lung mast cell heterogeneity.

Immunoprofiling reveals novel mast cell receptors and a continuous nature of human lung mast cell heterogeneity

BackgroundImmunohistochemical analysis of granule-associated proteases have revealed that human lungs 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 is yet to be performed.MethodsHuman lung mast cells were obtained from lung lobectomies and the expression of 332 cell surface markers were analyzed using flow cytometry and the LEGENDScreen™ kit. Markers that exhibited a high variance were selected for additional analyses to reveal whether they correlated and if discrete mast cell subpopulations were discernable.ResultsWe identified expression of 102 surface markers on human lung mast cells. Several markers showed a high continuous variation of expression within the mast cell population. Six of these markers correlated: SUSD2, CD49a, CD326, CD34, CD66 and HLA-DR. The expression of these markers also correlated to the size and granularity of the 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, out of which 23 have to our knowledge not previously described on human mast cells. Several of the newly described markers are known to be involved in sensing the microenvironment, and their identification can shed new light on mast cell functions. The exhaustive expression profiling of the 332 surface markers failed to detect distinct mast cell subpopulations. Instead, we demonstrate a continuous nature of human lung mast cell heterogeneity.

Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns

Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine urochordate Styela plicata, they have been designated as test cells. However, based on their morphological characteristics (including prominent cytoplasmic granules) and mediator content (including heparin, histamine, and neutral proteases), test cells are thought to represent members of the lineage known in vertebrates as mast cells. So this lineage presumably had important functions that preceded the development of antibodies, including IgE. Yet mast cells are best known, in humans, as key sources of mediators responsible for acute allergic reactions, notably including anaphylaxis, a severe and potentially fatal IgE-dependent immediate hypersensitivity reaction to apparently harmless antigens, including many found in foods and medicines. In this review, we briefly describe the origins of tissue mast cells and outline evidence that these cells can have beneficial as well as detrimental functions, both innately and as participants in adaptive immune responses. We also discuss aspects of mast cell heterogeneity and comment on how the plasticity of this lineage may provide insight into its roles in health and disease. Finally, we consider some currently open questions that are yet unresolved.