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.