title: Delayed eosinophil programmed cell death in vitro: a common feature of inhalant allergy and extrinsic and intrinsic atopic dermatitis.
abstract: The present studies were undertaken to characterize the potential role of eosinophil programmed cell death (PCD) in atopic diseases. Peripheral blood eosinophil PCD was found to be delayed in inhalant allergy (p < 0.05) and delayed to an even greater extent in atopic dermatitis (AD) (p < 0.0001) when compared to nonatopic subjects. There was no difference in the occurrence of PCD between the extrinsic and the intrinsic type of AD, pointing to a secondary role of specific sensitization. Blockade of eosinophil PCD was not responsible for peripheral blood eosinophilia, because we found no obvious relationship of eosinophil survival to blood eosinophil count. Eosinophil supernatants of more patients with AD than of patients with inhalant allergy dose-dependently inhibited PCD in nonatopic eosinophils, and it was shown that this effect was possibly due to autocrine production of granulocyte-macrophage-colony stimulating factor, probably IL-5. Eosinophil expression of CD95 (Fas antigen) did not change over time in culture and was not modulated by cytokines prolonging eosinophil survival. In contrast, IL-3, IL-5, and granulocyte-macrophage-colony stimulating factor caused an upregulated expression of CD69. However, in AD, CD69 on eosinophils was upregulated without the need of exogenous growth factor or factors over time in culture, thus confirming an autocrine production of proeosinophilic cytokines. In conclusion, our data clearly indicate that eosinophil PCD is markedly delayed in the so-called atopic diseases irrespective of allergen sensitization and suggest that this effect is mediated by the autocrine production of growth factors by eosinophils.
authors.affiliation: Department of Dermatology, Hannover Medical School, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wedi
authors.forename: U
authors.initials: U
authors.lastname: Raap
authors.forename: H
authors.initials: H
authors.lastname: Lewrick
authors.forename: A
authors.initials: A
authors.lastname: Kapp
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis / Q000502:physiology*; D001249:Asthma / Q000097:blood* / Q000473:pathology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D004247:DNA / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000097:blood* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000473:pathology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D037181:Lectins, C-Type; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008875:Middle Aged; D009707:Nucleosomes / Q000378:metabolism; D012222:Rhinitis, Atrophic / Q000097:blood* / Q000378:metabolism; D019014:fas Receptor / Q000096:biosynthesis; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D004247:DNA; D007073:Immunoglobulin E; D037181:Lectins, C-Type; D009707:Nucleosomes; D019014:fas Receptor; D000099192:CD69 Antigens