Eosinophils from asthmatics release IL-5 in an autocrine fashion to prevent apoptosis through upregulation of Bcl-2 expression.
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.
Huang
Chien-Da
CD
Department of Thoracic Medicine II, Chang Gung Memorial Hospital, Taipei, Taiwan.
Wang
Chun-Hua
CH
Liu
Chien-Ying
CY
Lin
Shu-Min
SM
Chou
Chun-Liang
CL
Liu
Wen-Te
WT
Lin
Horng-Chyuan
HC
Kuo
Han-Pin
HP
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
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