1.0 Introduction
Humans have battled with allergies for decades. The concept of allergies was first introduced in the early twentieth century by an Austrian scientist named von Pirquet, describing that an allergy occurs when exogenous substances (allergens) induce a change in reactivity in an individual’s immune system, leading to hypersensitive reactions1. Typical allergens are found in a wide range of environmental substances varying in their nature and source, including food allergens, aeroallergens like pollen, mites, and dust, as well as chemical allergens like dyes, creams and skincare products (2). Common allergic diseases include atopic eczema (dermatitis), rhinitis, allergic asthma, drug, and food allergies. Allergic diseases are considered a worldwide severe health issue, and their prevalence comprises a substantial percentage of the population. Rhinitis and food allergies affect 10-30% and 8% of the population worldwide, respectively, while skin allergies such as eczema have a lifetime prevalence of 20% worldwide 2. Allergy symptoms range from mild, such as itchiness, hives, watery eyes, and a runny nose, to life-threatening outcome, depending on the hyperreactivity of the immune system. The lethal and exaggerated allergic reaction known as anaphylaxis is the primary cause of death in allergic patients 3.
Currently, the most well-known curative treatment for IgE-mediated allergies is allergen-specific immunotherapy (AIT). This form of therapy involves subcutaneous administration of gradually increasing quantities of a patient’s corresponding allergen until an ideal dose capable of stimulating immune tolerance toward the allergen is achieved 4. Immunologic improvements in patients subjected to AIT are associated with the production of T regulatory cells that induce the anti-inflammatory cytokine IL)-10, which causes an early decrease in mast cells and basophil activation and the subsequent reduction of inflammatory mediators such as histamine5. Despite the efficacy of AIT, the development of immune tolerance in patients is still an evolving area. Other short-lived first-line treatments widely used consist of inhalation of corticosteroids, β-adrenergic agonists, and leukotriene modifiers in allergic asthma, or the avoidance of the food allergen and treatment with antihistamines for mild symptoms of food allergies are available6,7. However, these forms of treatment merely alleviate allergy symptoms rather than target the underlying pathology of the disorder.
The use of in vitro mast cell models may be able to answer and resolve some of the issues faced with current treatment. Mast cells have been considered the main effector cells in allergic reactions, and as a result, they have become attractive candidates in the study of allergenicity and sensitization mechanisms. Mast cells originate from multipotent hematopoietic stem cells that are mainly distributed in blood vessels located at the host-environment interface, such as the skin, airways, and gastrointestinal tract. Their localization in the body makes them one of the first immune cells to interact with incoming allergens 3. As described previously, mast cells play a central role during an allergic reaction. As mast cells are replete with the high-affinity IgE receptor FcεRI, binding of allergen-specific IgE stimulates mast cell degranulation releases prestored pro-inflammatory mediators such as histamine, serotonin and proteases as well as de novo synthesis of inflammatory mediators such as leukotriene and prostaglandins 8. This surge in the excessive release of such mediators rapidly triggers anaphylactic shocks. As mast cells differentiate in the peripheral tissues from progenitor cells in the bone marrow, CD34+ myeloid progenitor cells, derived from buffy coats, cord blood, or bone marrow, have been used as the primary source for the generation of mast cellsin vitro 9. However, in vitro research using human mast cells pose several challenges such as having low proliferative activity and the differentiation steps occurring physiologically in tissues are time-consuming, difficult and expensive to recapitulate in vitro 10. As such, several commercial human mast cell lines have been generated such as the HMC-1 (human mast cell line 1), LAD2 (Laboratory of allergic diseases 2) and LUVA (Laboratory of University of Virginia) as well as rodent mast cell lines such as the RBL-2H3 (rat basophilic leukemia-2H3) cell line which are routinely used as in vitro allergy models depending on their specific advantages and limitations 11. Although no model has been able to fully replicate human mast cell phenotypes, given the right culturing conditions and experimental setup, each model may possess some benefit over the selection of others.
To our knowledge, there is relatively limited data on large-scale tabulated data regarding the usage of mast cell line models. Hence, in this paper, three common mast cell line models (HMC-1, LAD2, and RBL-2H3) used in allergy-related studies are systematically reviewed with respect to their culturing conditions, types of inducers used, and inducing conditions. We also draw comparative tabulations and reasonings on the type of mast cell line used in respect of the type of laboratory conditions and experimental purposes. The review seeks to provide researchers with details on the characteristics and mechanisms of each mast cell model to aid in the proper selection of models for future studies.