Different anti-apoptotic effects of normal and asthmatic serum on normal eosinophil apoptosis depending on house dust mite-specific IgE.
We investigated the effect of asthmatic serum on constitutive eosinophil apoptosis in normal subjects. Eosinophil apoptosis in normal subjects was inhibited by asthmatic serum but not normal serum. In a detailed analysis based on the presence of house dust mite (HDM) IgE, HDM IgE-positive (+) asthmatic serum was more effective for eosinophil apoptosis than that of HDM IgE-negative (-) asthmatic serum. HDM IgE+ asthmatic serum inhibited both HDM IgE- and HDM IgE+ normal eosinophil apoptosis, and HDM IgE- asthmatic serum suppressed eosinophil apoptosis of HDM IgE+ normal. HDM IgE- normal serum did not inhibit either HDM IgE- or HDM IgE+ normal eosinophil apoptosis, and HDM IgE+ normal serum inhibited HDM IgE+ normal eosinophil apoptosis. The kind of HDM IgE (Dermatophagoides pteronissinus-specific IgE and Dermatophagoides farinae-specific IgE) was not related to the effect of asthmatic serum on eosinophil apoptosis. Extracts of DP and DF, Der p1, and Der p2, were not effective for eosinophil apoptosis. HDM IgE+ asthmatic serum inhibited cleavage of procaspase 9 and procaspase 3. Asthmatic serum induced Akt and ERK phosphorylation, and ERK activation was suppressed by AKTi. Taken together, asthmatic serum inhibited normal eosinophil apoptosis via PI3K/Akt/ERK cascade. The novel approach taken in this study provided better insight into HDM-associated anti-apoptotic mechanism of eosinophils in patients with asthma.
Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Taejon, 301-746, Republic of Korea.
In Sik
IS
Kim
Mi Jin
MJ
Kim
Do Hyung
DH
Kim
Eugene
E
Choi
Ji-Sook
JS
Lee
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001249:Asthma / Q000097:blood* / Q000276:immunology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004789:Enzyme Activation; D004804:Eosinophils / Q000201:enzymology / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D007073:Immunoglobulin E / Q000276:immunology*; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology*; D013045:Species Specificity
D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D053453:Caspase 9