Unique activation status of peripheral blood mononuclear cells at acute phase of Kawasaki disease

Ikeda, Kazuyuki; Yamaguchi, Kenichiro; Tanaka, Tamami; Mizuno, Yumi; Hijikata, Atsushi; Ohara, Osamu; Takada, Hidetoshi; Kusuhara, Koichi; Hara, Toshiro

doi:10.1111/j.1365-2249.2009.04073.x

Cited by 72 publications

(66 citation statements)

References 28 publications

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“…38 A monocyte marker CD64 was also significantly upregulated in peripheral blood mononuclear cell transcriptomes of patients with acute KD. 39 Thus, monitoring the precursor monocytes in patients may be a novel diagnostic option for KD.…”

Section: Arterioscler Thromb Vasc Biolmentioning

confidence: 99%

Identification of Pathogenic Cardiac CD11c ⁺ Macrophages in Nod1-Mediated Acute Coronary Arteritis

Motomura

Kanno

Asano

et al. 2015

ATVB

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Objective— Nod1 is an intracellular pattern recognition receptor for bacterial peptidoglycan fragments. We previously reported that a synthetic Nod1 ligand, FK565, induced acute coronary arteritis in mice similar to that of Kawasaki disease. However, the molecular mechanisms underlying this characteristic inflammation have remained elusive. Approach and Results— We found that CD11c + MHC class II + cells accumulated in the heart of FK565-treated mice before arteritis development. Morphological features and gene expression signatures of the cardiac CD11c + MHC class II + cells suggested that this population is closely related to macrophages, and thus, we designated them cardiac CD11c + macrophages. Nod1 in nonhematopoietic cells, rather than hematopoietic cells, was required for the increase of cardiac CD11c + macrophages and arteritis development. Among nonhematopoietic cells, cardiac endothelial cells produced a large amount of chemokines in response to FK565. Endothelial cell–specific blockade of Nod1 signaling suppressed FK565-induced expression of these chemokines, accumulation of cardiac CD11c + macrophages, and subsequent coronary arteritis development. We also found that CCR2 + Ly6C hi inflammatory monocytes in peripheral blood supplied precursors of cardiac CD11c + macrophages. CCR2-deficient mice or pertussis toxin–treated mice exhibited decreased numbers of cardiac CD11c + macrophages and reduced arteritis. Conclusions— These results suggest that Ly6C hi monocytes are recruited to FK565-activated endothelial cells to generate cardiac CD11c + macrophages, which play a pivotal role in the pathogenesis of acute coronary arteritis.

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Section: Arterioscler Thromb Vasc Biolmentioning

confidence: 99%

Identification of Pathogenic Cardiac CD11c ⁺ Macrophages in Nod1-Mediated Acute Coronary Arteritis

Motomura

Kanno

Asano

et al. 2015

ATVB

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“…8,9 A selective NOD1 ligand, FK565, but not a selective NOD2 ligand, muramyl dipeptide (MDP), induced nitric oxide synthase-II protein/activity and vascular hyporeactivity ex vivo and shock in vivo. 10 Because innate immunity has been suggested to be involved in the pathogenesis or pathophysiology of cardiovascular diseases in adults, 7 as well as vasculitis in Kawasaki disease (KD) in children, 11 we have investigated the effects of stimulants for innate immune receptors, especially TLRs and NODs, on human artery endothelial cells in vitro and murine arteries in vivo. We found the stimulatory effects of pure NOD1 and NOD2 ligands on coronary artery endothelial cells in vitro and the induction of coronary arteritis by oral or parenteral administration of a pure selective NOD1 ligand with or without a microbial component in mice in vivo.…”

mentioning

confidence: 99%

Nod1 Ligands Induce Site-Specific Vascular Inflammation

Nishio

Kanno

Onoyama

et al. 2011

ATVB

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Objective-The goal of this study was to investigate the effects of stimulants for a nucleotide-binding domain, leucine-rich repeat-containing (NLR) protein family on human artery endothelial cells and murine arteries. Methods and Results-Human coronary artery endothelial cells were challenged in vitro with microbial components that stimulate NLRs or Toll-like receptors. We found stimulatory effects of NLR and Toll-like receptor ligands on the adhesion molecule expression and cytokine secretion by human coronary artery endothelial cells. On the basis of these results, we examined the in vivo effects of these ligands in mice. Among them, FK565, 1 of the nucleotide-binding oligomerization domain (Nod)-1 ligands induced strong site-specific inflammation in the aortic root. Furthermore, coronary arteritis/valvulitis developed after direct oral administration or ad libitum drinking of FK565. The degree of the respective vascular inflammation was associated with persistent high expression of proinflammatory chemokine/ cytokine and matrix metallopeptidase (Mmp) genes in each tissue in vivo by microarray analysis. Conclusion-This is the first coronary arteritis animal model induced by oral administration of a pure synthetic Nod1ligand. The present study has demonstrated an unexpected role of Nod1 in the development of site-specific vascular inflammation, especially coronary arteritis. These findings might lead to the clarification of the pathogenesis and pathophysiology of coronary artery disease in humans. Key Words: coronary artery disease Ⅲ immune system Ⅲ Kawasaki disease Ⅲ pathology Ⅲ coronary arteritis Ⅲ inflammation G erm-line encoded pattern-recognition receptors of the innate immune system sense exogenous microbial components and endogenous danger signals to protect the host. [1][2][3][4] The pattern-recognition receptors include Toll-like receptors (TLRs), retinoic acid-inducible gene (RIG)-I-like receptors, the leucine-rich repeat-containing (NLR) protein family, and as-yet-unidentified pattern-recognition receptors that recognize double-stranded DNA. 1,3 The TLR, RIG-I-like receptor, and NLR families consist of 10 (human), 3, and more than 20 members, respectively. 1,3,4 In the cardiovascular system, endothelial cells are usually the first among the structural cells to sense microbial components through pattern-recognition receptors. Human endothelial cells express functional innate immune receptors, such as TLRs and NLRs. 5,6 There is a line of evidence that activation of TLRs, especially TLR4 and TLR2, contributes to the development and progression of cardiovascular diseases, including atherosclerosis, cardiac dysfunction in sepsis, and congestive heart failure. 7 With respect to NLRs, only a limited number of studies have shown that human endothelial cells express functional NLRs, nucleotide-binding oligomerization domain 1 (NOD1) and NOD2. Chlamydophila pneumoniae and Listeria monocytogenes elicited NOD1-dependent interleukin (IL)-8 production in endothelial cells. 8,9 A selective NOD1 ligand, FK565, ...

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“…In recent studies, the involvement of TLR signaling and NOD-like receptor signaling in the pathophysiology of the acute phase of KD has been considered (14,15). In addition, based on a study reporting the repression of increases in the expression of NOD1 and NOD2 mRNA in mice macrophages by anti-TLR or anti-TNF-α antibodies, it can be assumed that the expression of NOD mRNA results from TNF-α production, possibly via TLR signaling (16).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional regulation by infliximab therapy in kawasaki disease patients with immunoglobulin resistance

et al. 2014

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Background: Infliximab (IFX), a known monoclonal antibody against tumor necrosis factor-α (TNF-α), is used to treat Kawasaki disease (KD) patients with intravenous immunoglobulin (IVIG) resistance. The transcriptional modulation of inflammation following IFX therapy has not been reported in KD patients. Methods: We investigated the transcript abundance profiles in whole blood obtained from eight IVIG-resistant KD subjects treated with IFX therapy using microarray platforms and compared them with those in initially IVIG-responsive subjects. A pathway analysis was performed using WikiPathways to search for the biological pathways of the transcript profiles. Four transcripts changed by IFX therapy were subsequently validated using quantitative real-time polymerase chain reaction. results: The pathway analysis showed the reduced abundance of transcripts in the nucleotide-binding oligomerization domain, matrix metalloproteinase (MMP), and inflammatory cytokine pathways and the increased abundance of transcripts in the T-cell receptor, apoptosis, TGF-β, and interleukin-2 pathways. Additionally, the levels of four transcripts (peptidase inhibitor-3, MMP-8, chemokine receptor-2, and pentraxin-3) related to KD vasculitis and IVIG resistance decreased after IFX therapy. conclusion: The administration of IFX was associated with both the signaling pathways of KD inflammation and several transcripts related to IVIG resistance factors. These findings provide strong theoretical support for the use of IFX in KD patients with IVIG resistance.

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Unique activation status of peripheral blood mononuclear cells at acute phase of Kawasaki disease

Cited by 72 publications

References 28 publications

Identification of Pathogenic Cardiac CD11c ⁺ Macrophages in Nod1-Mediated Acute Coronary Arteritis

Identification of Pathogenic Cardiac CD11c ⁺ Macrophages in Nod1-Mediated Acute Coronary Arteritis

Nod1 Ligands Induce Site-Specific Vascular Inflammation

Transcriptional regulation by infliximab therapy in kawasaki disease patients with immunoglobulin resistance

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Unique activation status of peripheral blood mononuclear cells at acute phase of Kawasaki disease

Cited by 72 publications

References 28 publications

Identification of Pathogenic Cardiac CD11c + Macrophages in Nod1-Mediated Acute Coronary Arteritis

Identification of Pathogenic Cardiac CD11c + Macrophages in Nod1-Mediated Acute Coronary Arteritis

Nod1 Ligands Induce Site-Specific Vascular Inflammation

Transcriptional regulation by infliximab therapy in kawasaki disease patients with immunoglobulin resistance

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Identification of Pathogenic Cardiac CD11c ⁺ Macrophages in Nod1-Mediated Acute Coronary Arteritis

Identification of Pathogenic Cardiac CD11c ⁺ Macrophages in Nod1-Mediated Acute Coronary Arteritis