Introduction
Chronic spontaneous urticaria (CSU) is
considered as the most common form of chronic urticaria, usually
persistent, with symptoms that significantly impact the quality of life
of patients.1 Mast cells are the main effector cells
in urticaria, and their degranulation leads to the immediate release of
mediators such as histamine, tryptase, chymase, and proteases, as well
as prostaglandins, leukotrienes, and cytokines.2,3Mast cells and basophils interact with various cells of the urticaria
lesion microenvironment such as eosinophils, lymphocytes, and
macrophages.2,3
Macrophages play a pivotal role in the innate immunity, and are able to
secrete various proteins with numerous functions.4,5,6The present study was based on the hypothesis that macrophages are
involved in CSU unresponsive to antihistamines, which would contribute
to the severity and perpetuation of the disease.4,5
Macrophages were selected as target cells because in a previous study
with immunoelectron microscopy, we observed cellular interaction in the
microvascular unit of the dermis, where Factor XIIIa+dermal dendrocytes phagocytosed the granules extruded by mast cells, in
an active cellular interaction.4
Recently, two phenotypic macrophage variants, called M1 and M2, have
been characterized in several studies, which express the killer and
repair functions dependent on the stimulus and environment to which
these cells are exposed.5,6 The M1 and M2 responses
are described as having contradictory properties, that is “killing or
repairing,” which are essential in the host’s defense mechanisms and
activate the opposite TH1 or TH2 responses.5,6,7 The
denomination M1 and M2 macrophages were specifically selected for the
type of response they can orchestrate, that is, the M1 macrophage
promotes the TH1 response and is considered as tumoricidal, whereas the
M2 macrophage promotes a TH2 response and is considered as
immunosuppressive.6 Considering that macrophages
recognize a specific situation, they are able to develop an adequate
response to the stimulus.5-7
In studies with macrophage populations, it was observed that chronic
diseases or cancers present a predominantly M2
population.6 The M2 phenotype predominates or leads to
a worse treatment response in eosinophilic diseases such as nasal
polyposis and allergic diseases such as asthma.7-13Accordingly, we aimed to characterize the macrophage subpopulation
present in CSU.
Objectives: To characterize
the presence and phenotype of macrophages in lesions of CSU patients
nonresponsive to treatment with antihistamines at optimized doses
(maximum recommended doses) and to compare the macrophage phenotype
observed on the skin with clinical and laboratory parameters such as
age, gender, urticaria time, C-reactive protein (CRP) and total serum
IgE, in addition to response to the autologous serum skin test (ASST).