title: sCD48 is anti-inflammatory in Staphylococcus aureus Enterotoxin B-induced eosinophilic inflammation.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Faculty of Medicine, Pharmacology & Experimental Therapeutics Unit, Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: R S
authors.initials: RS
authors.lastname: Gangwar
authors.affiliation: Faculty of Medicine, Pharmacology & Experimental Therapeutics Unit, Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: F
authors.initials: F
authors.lastname: Levi-Schaffer
mesh_terms: D000818:Animals; D000071178:CD48 Antigen / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000378:metabolism*; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000209:etiology / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D007958:Leukocyte Count; D051379:Mice; D010538:Peritonitis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010740:Phospholipases; D011485:Protein Binding; D059748:Proteolysis; D013203:Staphylococcal Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D000071178:CD48 Antigen; D004768:Enterotoxins; C031818:enterotoxin B, staphylococcal; D010740:Phospholipases
keywords: CD48; SEB; eosinophils, inflammation; peritonitis