Tartrate-Resistant Acid Phosphatase 5 (TRAP5) Promotes Eosinophil Migration During Allergic Asthma.

Abstract

Allergic asthma is characterized by type 2 inflammation and eosinophilia. Tartrate-resistant acid phosphatase 5 (TRAP5/ACP5) is a metallophosphatase expressed by alveolar macrophages that dephosphorylates osteopontin (OPN), a phosphoglycoprotein with increased expression in asthma. To investigate the role of TRAP5 during asthma, we used a murine model of ovalbumin (OVA) induced allergic airway inflammation as well as IL-33 induced airway inflammation including Trap5^-/- and wild-type (WT) mice. Histological analyses of murine lung revealed that OVA-induced inflammation induced the formation of inflammatory lesions and increased mucus production in both WT and Trap5^-/- mice. However, lower cytokine levels (including IL-5 and IL-13) were detected by multiplex immunoassay in Trap5^-/- mice after OVA-induced inflammation. Furthermore, qPCR analysis detected different gene expression profile of Trap5^-/-/OVA mice, including upregulation of Il-17a and downregulation of Il-33. Lower eosinophil numbers were measured in bronchoalveolar lavage fluid of Trap5^-/-/OVA mice using flow cytometry analysis, whereas immunofluorescence staining revealed high eosinophil number in lung tissue of both groups with OVA challenge. In the IL-33 model of type 2 inflammation, both WT and Trap5^-/- mice showed similar inflammatory responses with regard to cytokine levels and cell recruitment patterns. In vitro, eosinophil chemotaxis was facilitated by non-phosphorylated but not phosphorylated OPN, an effect inhibited by an α4β1 integrin inhibitor. The results suggest that TRAP5 is important in the recruitment of immune cells, including eosinophils, as well as in shaping the profile and amplification of the inflammatory response during allergic airway inflammation. Thus, TRAP5 may serve as a therapeutic target in allergic asthma. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).