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Background CD48 is a membrane receptor ( mCD48) on eosinophils and mast cells and exists in a soluble form ( sCD48). CD48 has a pivotal role in murine asthma and in the proinflammatory interactions of mast cells with eosinophils via its ligand CD244. Thus, CD48 might be important in human asthma. Methods Therefore, two separate cohorts ( IL and UK) comprising mild, moderate, and severe asthma and healthy volunteers were evaluated for blood leukocyte mCD48 expression and sCD48 in serum. Asthmatic bronchial biopsies were immunostained for CD48. sCD48 effect on CD244-dependent eosinophil activation was evaluated. Results Eosinophil mCD48 expression was significantly elevated in moderate while downregulated in severe asthma. mCD48 expression on B, T, and NK cells and monocytes in severe asthma was significantly increased. sCD48 levels were significantly higher in mild while reduced in severe asthma. sCD48 optimal cutoff values for differentiating asthma from health were identified as >1482 pg/ml ( IL) and >1619 pg/ml ( UK). In asthmatic bronchial biopsies, mCD48 was expressed predominantly by eosinophils. sCD48 inhibited anti- CD244-induced eosinophil activation. Conclusions mCD48 and sCD48 are differentially expressed in the peripheral blood of asthma patients of varying severity. sCD48 inhibits CD244-mediated eosinophil activation. These findings suggest that CD48 may play an important role in human asthma. [ABSTRACT FROM AUTHOR]

Background Allergy is characterized by eosinophilia and an increased susceptibility to microbial infection. Atopic dermatitis ( AD) is typically associated with Staphylococcus aureus ( SA) colonization. Some of the mechanisms by which SA and its exotoxins interact with eosinophils remain elusive. CD48, a glycosylphosphatidylinositol-anchored receptor belonging to the CD2 family, participates in mast cells - SA stimulating cross-talk, facilitates the formation of the mast cell/eosinophils effector unit and as expressed by eosinophils, mediates experimental asthma. Objective To investigate the role of CD48 expressed on human peripheral blood and mouse bone marrow-derived eosinophils ( BMEos) in their interaction with heat-killed SA and its three exotoxins, Staphylococcal enterotoxin B ( SEB), protein A (PtA) and peptidoglycan ( PGN). Methods Eosinophils were obtained from human peripheral blood and BM of WT and CD48−/− mice. SA was heat killed and eosinophils- SA/exotoxins interactions were analyzed by confocal microscopy, adhesion and degranulation, cell viability, cytokine release and cell signalling. In addition, peritonitis was induced by SEB injection into CD48−/− and WT mice. CD48 expression was studied in AD patients' skin and as expressed on their leucocytes in the peripheral blood. Results We provide evidence for the recognition and direct physical interaction between eosinophils and SA/exotoxins. Skin of AD patients showed a striking increase of eosinophil-associated CD48 expression while on peripheral blood leucocytes it was down-regulated. SA/exotoxins enhanced CD48 eosinophil expression, bound to CD48 and caused eosinophil activation and signal transduction. These effects were significantly decreased by blocking CD48 on human eosinophils or in BMEos from CD48−/− mice. We have also explored the role of CD48 in a SEB-induced peritonitis model in CD48−/− mice by evaluating inflammatory peritoneal cells, eosinophil numbers and activation. Conclusions These data demonstrate the important role of CD48 in SA/exotoxins-eosinophil activating interactions that can take place during allergic responses and indicate CD48 as a novel therapeutic target for allergy and especially of AD. [ABSTRACT FROM AUTHOR]