Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Padra, Medea LU ; Bergwik, Jesper LU ; Adler, Anna LU ; Marcoux, Genevieve LU ; Bhongir, Ravi K.V. LU orcid ; Papareddy, Praveen LU orcid and Egesten, Arne LU (2025) In American Journal of Respiratory Cell and Molecular Biology 73(4). p.612-622
Abstract

Allergic asthma is characterized by Type 2 inflammation and eosinophilia. Tartrate-resistant acid phosphatase 5 (TRAP5; also referred to as acid phosphatase 5 [ACP5]) is a metallophosphatase expressed by alveolar macrophages that dephosphorylates osteopontin, 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 Trap52/2 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 Trap52/2 mice.... (More)

Allergic asthma is characterized by Type 2 inflammation and eosinophilia. Tartrate-resistant acid phosphatase 5 (TRAP5; also referred to as acid phosphatase 5 [ACP5]) is a metallophosphatase expressed by alveolar macrophages that dephosphorylates osteopontin, 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 Trap52/2 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 Trap52/2 mice. However, lower cytokine levels (including IL-5 and IL-13) were detected by multiplex immunoassay in Trap52/2 mice after OVA-induced inflammation. Furthermore, quantitative PCR analysis detected different gene expression profiles of Trap52/2 /OVA mice, including upregulation of Il-17a and downregulation of Il-33. Lower eosinophil numbers were measured in BAL fluid of Trap52/2 /OVA mice using flow cytometry analysis, whereas immunofluorescence staining revealed a high eosinophil number in lung tissue of both groups with OVA challenge. In the IL-33 model of Type 2 inflammation, both WT and Trap52/2 mice showed similar inflammatory responses with regard to cytokine levels and cell recruitment patterns. In vitro, eosinophil chemotaxis was facilitated by nonphosphorylated, but not phosphorylated, osteopontin, an effect inhibited by an a4b1 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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
asthma, eosinophils, IL-33, osteopontin, TRAP5/ACP5
in
American Journal of Respiratory Cell and Molecular Biology
volume
73
issue
4
pages
11 pages
publisher
American Thoracic Society
external identifiers
  • scopus:105017662732
  • pmid:40173299
ISSN
1044-1549
DOI
10.1165/rcmb.2024-0304OC
language
English
LU publication?
yes
id
fda8b816-bf5e-4fe8-a855-f32d2c1e3332
date added to LUP
2025-11-25 14:50:25
date last changed
2025-11-26 03:01:29
@article{fda8b816-bf5e-4fe8-a855-f32d2c1e3332,
  abstract     = {{<p>Allergic asthma is characterized by Type 2 inflammation and eosinophilia. Tartrate-resistant acid phosphatase 5 (TRAP5; also referred to as acid phosphatase 5 [ACP5]) is a metallophosphatase expressed by alveolar macrophages that dephosphorylates osteopontin, 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<sup>2/2</sup> 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<sup>2/2</sup> mice. However, lower cytokine levels (including IL-5 and IL-13) were detected by multiplex immunoassay in Trap5<sup>2/2</sup> mice after OVA-induced inflammation. Furthermore, quantitative PCR analysis detected different gene expression profiles of Trap5<sup>2/2</sup> /OVA mice, including upregulation of Il-17a and downregulation of Il-33. Lower eosinophil numbers were measured in BAL fluid of Trap5<sup>2/2</sup> /OVA mice using flow cytometry analysis, whereas immunofluorescence staining revealed a 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<sup>2/2</sup> mice showed similar inflammatory responses with regard to cytokine levels and cell recruitment patterns. In vitro, eosinophil chemotaxis was facilitated by nonphosphorylated, but not phosphorylated, osteopontin, an effect inhibited by an a4b1 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.</p>}},
  author       = {{Padra, Medea and Bergwik, Jesper and Adler, Anna and Marcoux, Genevieve and Bhongir, Ravi K.V. and Papareddy, Praveen and Egesten, Arne}},
  issn         = {{1044-1549}},
  keywords     = {{asthma; eosinophils; IL-33; osteopontin; TRAP5/ACP5}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{612--622}},
  publisher    = {{American Thoracic Society}},
  series       = {{American Journal of Respiratory Cell and Molecular Biology}},
  title        = {{Tartrate-Resistant Acid Phosphatase 5 (TRAP5) Promotes Eosinophil Migration During Allergic Asthma}},
  url          = {{http://dx.doi.org/10.1165/rcmb.2024-0304OC}},
  doi          = {{10.1165/rcmb.2024-0304OC}},
  volume       = {{73}},
  year         = {{2025}},
}