title: Eosinophils from asthmatics release IL-5 in an autocrine fashion to prevent apoptosis through upregulation of Bcl-2 expression.
abstract: Interleukin (IL)-5 plays an important role in maintaining the survival of eosinophils via the specific alpha-subunit of its receptor. Apoptosis, a form of programmed cell death, is thought to represent a mechanism that promotes the resolution of eosinophilic inflammation in asthma. The aim of our present study is to investigate whether IL-5 acts in an autocrine fashion on eosinophil apoptosis in asthmatics. Immunoreactivities of intracellular IL-5 and IL-5 receptor alpha-subunit (Ralpha) were detected uniquely on the eosinophils. The magnitude of IL-5 and IL-5 Ralpha expression on eosinophils was significantly higher in asthmatics than that of normal subjects (p<0.05) determined by flow cytometry. Apoptosis of eosinophils was measured by the propidium iodide staining method and DNA ladder. The percent of apoptotic eosinophils from asthmatics was significantly increased by coincubation with anti-hIL-5 Ralpha Ab (0.1, 0.5, and 2.5 microg/mL) for 1, 2, or 16 hours than was those of corresponding controls (p<0.05, n=8). However, there was no significant effect of anti-hIL-5 Ralpha Ab on eosinophil apoptosis in normal subjects. Furthermore, the expression of B-cell lymphoma-2 (Bcl-2) proteins was significantly inhibited by the anti-hIL-5 Ralpha Ab or antisense IL-5 oligonucleotides in asthmatics (p<0.05, n=8), but there was no significant change in eosinophils from normal subjects. This study demonstrates that eosinophils from asthmatics release IL-5 in an autocrine fashion to act on their own IL-5 receptors in prevention of apoptosis through the upregulation of Bcl-2 expression.
authors.affiliation: Department of Thoracic Medicine II, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Chien-Da
authors.initials: CD
authors.lastname: Huang
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Chien-Ying
authors.initials: CY
authors.lastname: Liu
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Lin
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chou
authors.forename: Wen-Te
authors.initials: WT
authors.lastname: Liu
authors.forename: Horng-Chyuan
authors.initials: HC
authors.lastname: Lin
authors.forename: Han-Pin
authors.initials: HP
authors.lastname: Kuo
mesh_terms: D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D019898:Autocrine Communication; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D020033:Protein Isoforms / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism; D053649:Receptors, Interleukin-5; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000906:Antibodies; D015848:Interleukin-5; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D019014:fas Receptor