Abstract
BackgroundThe calcium-binding protein S100A4 demonstrates important regulatory roles in many biological processes including tumorigenesis and inflammatory disorders such as allergy. However, the specific mechanism of the contribution of S100A4 to allergic diseases awaits further clarification.ObjectiveTo address the effect of S100A4 on the regulation of mast cell activation and its impact on allergy.MethodsBone marrow-derived cultured mast cells (BMMCs) were derived from wild-type (WT) or S100A4-/- mice for in vitro investigation. WT and S100A4-/- mice were induced to develop a passive cutaneous anaphylaxis (PCA) model, a passive systemic anaphylaxis (PSA) model, and an ovalbumin (OVA)-mediated mouse asthma model.ResultsFollowing OVA/alum-based sensitization and provocation, S100A4-/- mice demonstrated overall suppressed levels of serum anti-OVA IgE and IgG antibodies and proinflammatory cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung exudates. S100A4-/- mice exhibited less severe asthma signs which included inflammatory cell infiltration in the lung tissue and BALF, and suppressed mast cell recruitment in the lungs. Reduced levels of antigen reencounter-induced splenocyte proliferation in vitro were recorded in splenocytes from OVA-sensitized and challenged mice that lacked S100A4-/-. Furthermore, deficiency in the S100A4 gene could dampen mast cell activation both in vitro and in vivo, evidenced by reduced β-hexosaminidase release and compromised PCA and PSA reaction. We also provided evidence supporting the expression of S100A4 by mast cells.ConclusionS100A4 is required for mast cell functional activation, and S100A4 may participate in the regulation of allergic responses at least partly through regulating the activation of mast cells.
Highlights
Allergy is one of the most prevalent human diseases affecting the quality of life of about 20% of the global population, the incidence of which has been steadily increasing over the past decades
This increasing trend is notable for allergic asthma and rhinitis, which has led to an enormous socioeconomic burden worldwide [1]
The mast cell is defined as a critical regulator and effector in the development and exacerbation of allergic pathology because of their potential to secrete a variety of allergic mediators [6]
Summary
Allergy is one of the most prevalent human diseases affecting the quality of life of about 20% of the global population, the incidence of which has been steadily increasing over the past decades. This increasing trend is notable for allergic asthma and rhinitis, which has led to an enormous socioeconomic burden worldwide [1]. IgE-mediated mast cell degranulation initiates the early phase of an allergic response, resulting in pathologies, including increased epithelial permeability, mucous production, smooth muscle contraction, vasodilatation and neurogenic inflammation. The specific mechanism of the contribution of S100A4 to allergic diseases awaits further clarification
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