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).