How Relevant Are Bone Marrow-Derived Mast Cells (BMMCs) as Models for Tissue Mast Cells? A Comparative Transcriptome Analysis of BMMCs and Peritoneal Mast Cells

Abstract

Bone marrow-derived mast cells (BMMCs) are often used as a model system for studies of the role of MCs in health and disease. These cells are relatively easy to obtain from total bone marrow cells by culturing under the influence of IL-3 or stem cell factor (SCF). After 3 to 4 weeks in culture, a nearly homogenous cell population of toluidine blue-positive cells are often obtained. However, the question is how relevant equivalents these cells are to normal tissue MCs. By comparing the total transcriptome of purified peritoneal MCs with BMMCs, here we obtained a comparative view of these cells. We found several important transcripts that were expressed at very high levels in peritoneal MCs, but were almost totally absent from the BMMCs, including the major chymotryptic granule protease Mcpt4, the neurotrophin receptor Gfra2, the substance P receptor Mrgprb2, the metalloprotease Adamts9 and the complement factor 2 (C2). In addition, there were a number of other molecules that were expressed at much higher levels in peritoneal MCs than in BMMCs, including the transcription factors Myb and Meis2, the MilR1 (Allergin), Hdc (Histidine decarboxylase), Tarm1 and the IL-3 receptor alpha chain. We also found many transcripts that were highly expressed in BMMCs but were absent or expressed at low levels in the peritoneal MCs. However, there were also numerous MC-related transcripts that were expressed at similar levels in the two populations of cells, but almost absent in peritoneal macrophages and B cells. These results reveal that the transcriptome of BMMCs shows many similarities, but also many differences to that of tissue MCs. BMMCs can thereby serve as suitable models in many settings concerning the biology of MCs, but our findings also emphasize that great care should be taken when extrapolating findings from BMMCs to the in vivo function of tissue-resident MCs.

MRGPRX2-Mediated Degranulation of Human Skin Mast Cells Requires the Operation of Gαi, Gαq, Ca++ Channels, ERK1/2 and PI3K—Interconnection between Early and Late Signaling

“…The authors reported that the reason for the discrepancy was a major difference between mouse and human MCs since only the latter depended on ERK for MRGPRX2-driven β-hexosaminidase and histamine release [54]. This was a notable finding since MC research is heavily biased towards the mouse, and makes vivid use of murine BMMCs, which differ not only from humans, but also from other murine MC types [72]. In our study, ERK involvement was found for both ex vivo and precultured skin MCs, yet it was stronger in the latter, suggesting that the cellular environment also plays a role in dictating the significance of ERK.…”

Harnessing the Anti-Tumor Mediators in Mast Cells as a New Strategy for Adoptive Cell Transfer for Cancer

“…In some cases, a pro- and anti-tumor effect was observed in the same tumors ( 67 , 113 , 114 ). In addition, differences in MC phenotypic and functional responses between mice and humans have been well documented ( 111 , 115 – 123 ). For example, Fcγ receptor expression and functional responses mediated by them on mouse and human MCs and monocytes are vastly different ( 124 – 126 ).…”

Mast Cell and Basophil Granule Proteases - In Vivo Targets and Function

“…The transcripts for the granule proteases are the most highly expressed transcripts in the mature MC where the expression levels can be in the range of several percent of the total transcriptome ( 1 , 16 , 22 ). In addition to MC tryptase and chymase, serine proteases belonging to the same family of trypsin/chymotrypsin related serine proteases have in mammals also been identified in basophils, neutrophils, cytotoxic T cells and natural killer (NK) cells but not in B cells, macrophages, red blood cells, platelets or dendritic cells and only at relatively low levels in eosinophils.…”