Induction of peripheral mononuclear cell apoptosis in asthmatic patients in remission.
Apoptosis regulates inflammatory cell survival in allergic inflammation, and decreased apoptosis contributes to the chronicity of inflammation. To investigate the mechanisms of onset and remission of mite-sensitive childhood asthma, we evaluated peripheral blood mononuclear cell apoptosis in patients with asthma and in remission. There was a similar percentage of hypodiploid cells in unstimulated mononuclear cell cultures from patients with active asthma (29.5+/-5.0%) and normal individuals (25.9+/-4.9%). In contrast, the percentage increased in patients in remission (44.5+/-3.2%). In Dermatophagoides farinae (Df) antigen-stimulated mononuclear cell, the stimulation index was lower in patients with active asthma (0.95+/-0.06%) than in normal individuals (1.31+/-0.16%). In contrast to active patients, the proportion of hypodiploid cells stimulated with Df in patients with remission was equivalent to that of normal controls. After phytohemaglutinin (PHA) stimulation, the percentage of hypodiploid cells in patients with active asthma (35.1+/-3.2%) was also lower than in normal individuals (48.5+/-4.3%) or patients in remission (49.5+/-5.7%). Apoptosis occurred predominantly in CD8+, but not CD4+, cells in patients in remission. Interleukin IL-2 inhibited apoptosis in Df-activated cells in normal individuals, whereas IL-2 did not inhibit apoptosis in cells from patients in remission as well as with active asthma. The expression of Fas receptors on resting mononuclear cells was similar in the three groups. However, Fas receptor expression in Df-stimulated mononuclear cells was greater in patients with active asthma than in healthy individuals. In patients with remission that was equivalent to healthy controls. The PHA increased Fas expression to a similar degree in the three groups. With regard to Fas ligand, the expression was lower in unstimulated cultured mononuclear cells from patients than in normal individuals. In patients in remission that was comparable to normal individuals. The Df stimulation upregulated the Fas ligand in patients with active asthma, and downregulated it in patients in remission. In conclusion, apoptosis in Df-stimulated mononuclear cells is impaired in patients with active asthma, while spontaneous apoptosis of CD8+ cells in vivo is augmented in patients in remission, and may be involved in the onset and remission of mite-sensitive asthma.
Noma
T
T
Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. nomatake@med.kitasato-u.ac.jp
Sugawara
Yoko
Y
Aoki
K
K
Kawano
Y
Y
Ishikawa
Y
Y
Matsuura
N
N
D000293:Adolescent; D000818:Animals; D017209:Apoptosis; D001249:Asthma / Q000276:immunology*; D002648:Child; D040001:Dermatophagoides farinae / Q000276:immunology; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor