Unique activation status of peripheral blood mononuclear cells at acute phase of Kawasaki disease.
Although Kawasaki disease (KD) is characterized by a marked activation of the immune system with elevations of serum proinflammatory cytokines and chemokines at acute phase, the major sources for these chemical mediators remain controversial. We analysed the activation status of peripheral blood mononuclear cells (PBMCs) by flow cytometry, DNA microarray and quantitative reverse transcription-polymerase chain reaction. The proportions of CD69+ cells in both natural killer cells and gammadeltaT cells at acute-phase KD were significantly higher than those at convalescent-phase KD. Microarray analysis revealed that five genes such as NAIP, IPAF, S100A9, FCGR1A and GCA up-regulated in acute-phase KD and the pathways involved in acute phase KD were related closely to the innate immune system. The relative expression levels of damage-associated molecular pattern molecule (DAMP) (S100A9 and S100A12) genes in PBMCs at acute-phase KD were significantly higher than those at convalescent-phase KD, while those of TNFA, IL1B and IL6 genes were not significantly different between KD patients and healthy controls. Intracellular production of tumour necrosis factor-alpha, interleukin-10 and interferon-gamma in PBMCs was not observed in KD patients. The present data have indicated that PBMCs showed a unique activation status with high expression of DAMP genes but low expression of proinflammatory cytokine genes, and that the innate immune system appears to play a role in the pathogenesis and pathophysiology of KD.
Ikeda
K
K
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ikeq@pediatr.med.kyushu-u.ac.jp
Yamaguchi
K
K
Tanaka
T
T
Mizuno
Y
Y
Hijikata
A
A
Ohara
O
O
Takada
H
H
Kusuhara
K
K
Hara
T
T
D000208:Acute Disease; D000328:Adult; D000954:Antigens, Surface / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003289:Convalescence; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D005802:Genes, MHC Class II; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D000954:Antigens, Surface; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins