sCD48 is anti-inflammatory in Staphylococcus aureus Enterotoxin B-induced eosinophilic inflammation

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.