3.0 HMC-1 cell line
The human mast cell 1 line (HMC-1) is a well-known model used in allergic and inflammatory disease studies. It was established from a mast cell leukemia patient, entailing a dedifferentiated, spindle-shaped hypogranular appearance 9,12. While it is considered an immature mast cell, the HMC-1 cell line shares a phenotype akin to human mast cells (HuMC). The expression of mast cell-associated markers (i.e., histamine, heparin, tryptase, and c-kit receptor) and a similar cell surface antigen profile render the HMC-1 cell line a strong candidate in allergy research13,14. HMC-1 can be further subdivided into HMC-1.1 (HMC560) and HMC-1.2 (HMC560, 816), depending on the location of the mutation in the c-kit receptor. HMC-1.1 possesses a substitution of glycine-560 to valine (V560G), while HMC-1.2 contains the V560G mutation and another substitution of valine-816 to aspartate (D816V) 15,16. These mutations in the c-kit receptor cause dysregulation in c-kit receptor expression, thus resulting in the survival of HMC-1 cell lines independent of stem cell factor (SCF) which is essential for mast cell proliferation, chemotaxis, activation, differentiation, and survival 17,18. This allows the usage of HMC-1 cells to be highly favorable in an in vitro mast cell research as they have a higher proliferative rate than other mast cell lines. The doubling time of the HMC-1 cell line (1-3 days) is described to be 10-fold faster than the LAD2 cell line (10-14 days)9,19. In addition, when compared between the two variant sublines, HMC-1.2 exhibits a higher proliferative rate than HMC-1.1 due to the presence of D816V mutation 20. This mutation leads to constitutive tyrosine kinase activation of the Kit receptor that causes a higher proliferation rate as compared to the HMC-1.1 which does not have the same mutation point21.
Despite sharing a phenotype akin to HuMCs, the HMC-1 cell line contains dissimilarities when compared to mature HuMCs. HMC-1 cell line has a low expression of mature HuMCs markers (i.e., tryptase and chymase), with the exception of c-kit and histamine, representing immature malignantly transformed mast cells 22. The binding of IgE to the high-affinity IgE receptor FcεRI is crucial for the activation and degranulation of mast cells 23. As such, the lack in surface expression of FcεRI in the HMC-1 cell line requires the usage of a physiological stimulus, such as phorbol myristate acetate (PMA), calcium ionophore (CI), and compound 48/80 (C48/80)24. Additionally, Mas-Related G-protein coupled Receptor X2 (MRGPRX2) is known to induce mast cell degranulation, contributing to pseudo-allergic reactions caused by small molecule drugs. The HMC-1 cell line, however, expresses lower levels of MRGPRX2 and poor degranulation activity than the LAD2 cell line and HuMCs. It is noted that latrunculin-B can be used to prompt MRGPRX2-mediated degranulation 9. Overall, the shortcomings of the HMC-1 cell line may potentially limit the insights available to mast cell activation studies. Yet, the high proliferative rate and stable phenotype render them a feasible model for extensive in vitrostudies.