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

15 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

Funding Information:
This work was supported by grants from MAARS EU 7th framework (number HEALTH-F2-2011-261366); Hebrew University of Jerusalem (Israel)-Drexel University (Philadelphia, PA, USA) Joint grant (number 0304917); Israel Science Foundation (grant number 213/05 and 472/15); and the Aimwell Charitable Trust (London, UK) to F Levi-Schaffer. RSG received the 'PBC postdoctoral fellowship for Indian and Chinese students' from The Hebrew University of Jerusalem, Israel. FLS is affiliated with the David R. Bloom Center of Pharmacy and the Adolph and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem.

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

Keywords

  • CD48
  • SEB
  • eosinophils, inflammation
  • peritonitis

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