TNF-related apoptosis-inducing ligand is involved in neutropenia of systemic lupus erythematosus.
Neutropenia is a common laboratory finding in systemic lupus erythematosus (SLE). However, the molecular mechanism of SLE neutropenia has not been fully explained. In this study, we examined whether TNF-related apoptosis-inducing ligand (TRAIL) is involved in the pathogenesis of SLE neutropenia using samples from SLE patients. Serum TRAIL levels in SLE patients with neutropenia were significantly higher than those of SLE patients without neutropenia and healthy volunteers. Serum TRAIL levels showed a significant negative correlation with neutrophil counts in SLE patients. The expression of TRAIL receptor 3 was significantly lower in SLE patients with neutropenia than in patients without neutropenia or in healthy volunteers. Treatment with glucocorticoids negated the decrease of TRAIL receptor 3 expression on neutrophils of SLE patients. TRAIL may accelerate neutrophil apoptosis of neutrophils from SLE patients, and autologous T cells of SLE patients, which express TRAIL on surface, may kill autologous neutrophils. Interferon gamma and glucocorticoid modulated the expression of TRAIL on T cells of SLE patients and also modulated the expression of cellular Fas-associating protein with death domain-like interleukin-1 beta-converting enzyme (FLICE)-inhibitory protein (cFLIP), an inhibitor of death receptor signaling, in neutrophils. Thus, our results provide a novel insight into the molecular pathogenesis of SLE neutropenia.
Department of Respiratory Medicine, National Minami-kyushu Hospital and Third Department of Internal Medicine, Kagoshima University Faculty of Medicine, Sakuragaoka, Japan. vega@xa2.so-net.ne.jp
Wataru
W
Matsuyama
Masuki
M
Yamamoto
Ikkou
I
Higashimoto
Ken-ichi
K
Oonakahara
Masaki
M
Watanabe
Kentarou
K
Machida
Teizo
T
Yoshimura
Nobutaka
N
Eiraku
Masaharu
M
Kawabata
Mitsuhiro
M
Osame
Kimiyoshi
K
Arimura
D000328:Adult; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000096:biosynthesis; D016022:Case-Control Studies; D003345:Corticosterone / Q000494:pharmacology; D005260:Female; D058851:GPI-Linked Proteins; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism; D017452:Receptors, IgG / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D011994:Recombinant Proteins / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D058851:GPI-Linked Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C108661:TNFRSF10C protein, human; C505653:TNFSF10 protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D003345:Corticosterone