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