Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen
James D. Nolin, … , William A. Altemeier, Teal S. Hallstrand
James D. Nolin, … , William A. Altemeier, Teal S. Hallstrand
Published November 2, 2017
Citation Information: JCI Insight. 2017;2(21):e94929. https://doi.org/10.1172/jci.insight.94929.
View: Text | PDF
Research Article Immunology Inflammation

Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen

  • Text
  • PDF
Abstract

Phospholipase A2 (PLA2) enzymes regulate the formation of eicosanoids and lysophospholipids that contribute to allergic airway inflammation. Secreted PLA2 group X (sPLA2-X) was recently found to be increased in the airways of asthmatics and is highly expressed in airway epithelial cells and macrophages. In the current study, we show that allergen exposure increases sPLA2-X in humans and in mice, and that global deletion of Pla2g10 results in a marked reduction in airway hyperresponsiveness (AHR), eosinophil and T cell trafficking to the airways, airway occlusion, generation of type-2 cytokines by antigen-stimulated leukocytes, and antigen-specific immunoglobulins. Further, we found that Pla2g10–/– mice had reduced IL-33 levels in BALF, fewer type-2 innate lymphoid cells (ILC2s) in the lung, less IL-33–induced IL-13 expression in mast cells, and a marked reduction in both the number of newly recruited macrophages and the M2 polarization of these macrophages in the lung. These results indicate that sPLA2-X serves as a central regulator of both innate and adaptive immune response to proteolytic allergen.

Authors

James D. Nolin, Ying Lai, Herbert Luke Ogden, Anne M. Manicone, Ryan C. Murphy, Dowon An, Charles W. Frevert, Farideh Ghomashchi, Gajendra S. Naika, Michael H. Gelb, Gail M. Gauvreau, Adrian M. Piliponsky, William A. Altemeier, Teal S. Hallstrand

×

Figure 1

Proteolytic allergens increase sPLA2-X in human and mouse airways.

Options: View larger image (or click on image) Download as PowerPoint
Proteolytic allergens increase sPLA2-X in human and mouse airways.
(A) F...
(A) Four individuals with asthma were challenged via the airways with aerosolized allergen, and levels of sPLA2-X protein were measured using time-resolved fluorescence immunoassay (TRFIA) in induced sputum at 7 hours and 24 hours after challenge. Mean ± SEM (n = 4/time point) with 1-way ANOVA. BL, baseline. (B) Whole lung Pla2g10 gene expression from WT and Pla2g10–/– (–/–) mice exposed to saline or HDM (n = 3/group). Mean ± SEM, Mann-Whitney test. (C) BALF sPLA2-X protein levels from WT and Pla2g10–/– mice exposed to HDM were analyzed via Western blot (20 μl/lane) and quantified using densitometry (n = 4 for saline [Sal] and 7 for HDM). Mean ± SEM, Mann-Whitney test. A.U., arbitrary units.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts