SCD48 is anti-inflammatory in Staphylococcus aureus Enterotoxin B-induced eosinophilic inflammation

R. S. Gangwar, F. Levi-Schaffer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background Staphylococcus aureus, one of the most important pathogens, is heavily associated with allergy. S. aureus and its toxins interact with eosinophils through CD48, a GPI-anchored receptor important in allergy mainly as expressed by the eosinophils (mCD48). CD48 can exist in a soluble form (sCD48). Our aim was to investigate SEB-induced regulation of eosinophil CD48 and the possible formation and role of sCD48 in SEB-mediated eosinophil activation in vitro and in vivo. Methods Human perIPheral blood eosinophils were activated by SEB with or without inhibitors for phospholIPases (PL) (-C or -D), or cycloheximide, or brefeldin A. We evaluated eosinophil activation (CD11b expression or EPO/IL-8 release), mCD48 (flow cytometry), sCD48 (ELISA), SEB binding to sCD48 (ELISA), and chemotaxis toward SEB. C57BL/6 mice were pre-injected (IP.) with sCD48, and then, peritonitis was induced by SEB injection; peritoneal lavages were collected after 48 h and analyzed by flow cytometry and ELISA. Results SEB-activated human eosinophils formed sCD48, directly correlating with CD11b expression, through cell-associated PL-C and -D. mCD48 remained stable due to up-regulation in CD48 transcrIPtion and cellular trafficking. sCD48 bound to SEB and down-regulated SEB stimulatory effects on eosinophils as assessed by EPO and IL-8 release and eosinophil chemotaxis toward SEB. sCD48 showed anti-inflammatory activity in a SEB-induced mouse peritonitis model. Conclusions SEB regulates CD48 dynamics on eosinophils. Our data indicate sCD48 as a SEB-induced 'decoy' receptor derived from eosinophil and therefore as a potential anti-inflammatory tool in S. aureus-induced eosinophil inflammation often associated with allergy.

Original languageAmerican English
Pages (from-to)829-839
Number of pages11
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume71
Issue number6
DOIs
StatePublished - 1 Jun 2016

Bibliographical note

Publisher Copyright:
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords

  • CD48
  • SEB
  • eosinophils, inflammation
  • peritonitis

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