FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation

Xiao Na Ge, Idil Bastan, Mythili Dileepan, Yana Greenberg, Sung Gil Ha, Kaylee A. Steen, David A. Bernlohr, Savita P. Rao, P. Sriramarao

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Fatty acid binding protein 4 (FABP4), a member of a family of lipid-binding proteins, is known to play a role in inflammation by virtue of its ability to regulate intracellular events such as lipid fluxes and signaling. Studies have indicated a proinflammatory role for FABP4 in allergic asthma although its expression and function in eosinophils, the predominant inflammatory cells recruited to allergic airways, were not investigated. We examined expression of FABP4 in murine eosinophils and its role in regulating cell recruitment in vitro as well as in cockroach antigen (CRA)-induced allergic airway inflammation. CRA exposure led to airway recruitment of FABP4-expressing inflammatory cells, specifically eosinophils, in wild-type (WT) mice. FABP4 expression in eosinophils was induced by TNF-α as well as IL-4 and IL-13. FABP4-deficient eosinophils exhibited markedly decreased cell spreading/formation of leading edges on vascular cell adhesion molecule-1 and significantly decreased adhesion to intercellular adhesion molecule-1 associated with reduced β2-integrin expression relative to WT cells. Furthermore, FABP4-deficient eosinophils exhibited decreased migration, F-actin polymerization, calcium flux, and ERK(1/2) phosphorylation in response to eotaxin-1. In vivo, CRA-challenged FABP4-deficient mice exhibited attenuated eosinophilia and significantly reduced airway inflammation (improved airway reactivity, lower IL-5, IL-13, TNF-α, and cysteinyl leukotriene C4 levels, decreased airway structural changes) compared with WT mice. In conclusion, expression of FABP4 in eosinophils is induced during conditions of inflammation and plays a proinflammatory role in the development of allergic asthma by promoting eosinophil adhesion and migration and contributing to the development of various aspects of airway inflammation.

Original languageEnglish (US)
Pages (from-to)L227-L240
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume315
Issue number2
DOIs
StatePublished - Aug 2018

Bibliographical note

Publisher Copyright:
© 2018 American Physiological Society. All rights reserved.

Keywords

  • Activation
  • Allergic asthma
  • Cell adhesion and migration
  • Eosinophils
  • Fatty acid binding protein 4

Fingerprint

Dive into the research topics of 'FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation'. Together they form a unique fingerprint.

Cite this