A pathological study on the efficacy of Syk inhibitors in a Candida albicans-induced aortic root vasculitis murine model.

Background: The activation of innate immunity may be involved in the development of Candida albicans-induced murine vasculitis, which resembles Kawasaki disease (KD) vasculitis. This study aimed to histologically clarify the time course of the development of vasculitis in this model in detail and to estimate the potential role of spleen tyrosine kinase (Syk) inhibitors in KD vasculitis.

Methods And Results: DBA/2 male mice were intraperitoneally injected with a vasculitis-inducing substance and treated with a Syk inhibitor (R788 or GS-9973).

Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease.

Background: Kawasaki disease (KD) is usually treated with high-dose intravenous immunoglobulin (IVIg) as severe infectious and other diseases. Due to issues that are associated with immunoglobulin preparation, such as the risk of possible contamination by infectious agents and limited blood banking resources, recombinant immunoglobulins are required. We developed a novel recombinant antibody drug candidate, "VasSF," based on the therapeutic effects it exerted on a mouse spontaneous crescentic glomerulonephritis model (SCG/Kj).

CDCP1 on Dendritic Cells Contributes to the Development of a Model of Kawasaki Disease.

The etiology and pathology of Kawasaki disease (KD) remain elusive. Cub domain-containing protein 1 (CDCP1), a cell-surface protein that confers poor prognosis of patients with certain solid tumors, was recently identified as one of the most significantly upregulated genes in SARS-CoV-2-infected children who developed systemic vasculitis, a hallmark of KD. However, a potential role of CDCP1 in KD has not previously been explored.

Coronary Vasculitis Induced in Mice by Cell Wall Mannoprotein Fractions of Clinically Isolated Candida Species.

Kawasaki disease (KD) is an inflammatory disease that was identified by Professor Tomisaku Kawasaki in 1961. Candida albicans-derived substances (CADS) such as the hot water extract of C. albicans and Candida water-soluble fractions (CAWS) induce coronary vasculitis similar to KD in mice.

Coronary Vasculitis Induced in Mice by the Cell Wall Mannoprotein of Candida krusei.

Kawasaki disease (KD) is an inflammatory disease that was identified by Professor Tomisaku Kawasaki in 1961. Candida albicans-derived substances, such as the hot water extract of C. albicans (CADS) and Candida water-soluble fraction (CAWS), induced coronary vasculitis similar to KD in mice.

Abrogation of lysophosphatidic acid receptor 1 ameliorates murine vasculitis.

Background: Lysophosphatidic acid (LPA), generated by autotaxin (ATX), is a bioactive lipid mediator that binds to the receptors (LPA), and serves as an important mediator in inflammation. Previous studies have demonstrated that LPA-LPA cascade contributes to arthritis and skin sclerosis. In this study, we examined the role of LPA signals in murine Candida albicans water-soluble fraction (CAWS)-induced vasculitis.

N-Terminal (1→3)-β-d-Glucan Recognition Proteins from Insects Recognize the Difference in Ultra-Structures of (1→3)-β-d-Glucan.

Recognition of (1→3)-β-d-glucans (BGs) by invertebrate β-1,3-d-glucan recognition protein (BGRP) plays a significant role in the activation of Toll pathway and prophenoloxidase systems in insect host defense against fungal invasion. To examine the structure diversity of BGRPs for the recognition of physiochemically different BGs, the binding specificity of BGRPs cloned from four different insects to structure different BGs was characterized using ELISA. Recombinant BGRPs expressed as Fc-fusion proteins of human IgG1 bound to the solid phase of BGs.

Dectin-2-induced CCL2 production in tissue-resident macrophages ignites cardiac arteritis.

Environmental triggers, including those from pathogens, are thought to play an important role in triggering autoimmune diseases, such as vasculitis, in genetically susceptible individuals. The mechanism by which activation of the innate immune system contributes to vessel-specific autoimmunity in vasculitis is not known. Systemic administration of Candida albicans water-soluble extract (CAWS) induces vasculitis in the aortic root and coronary arteries of mice that mimics human Kawasaki disease.

Recognition of alpha-mannan by dectin 2 is essential for onset of Kawasaki disease-like murine vasculitis induced by cell-wall polysaccharide.

Using a murine model of systemic Kawasaki disease (KD)-like vasculitis induced by cell-wall-derived mannan · β-glucan · protein complexes, the objective was to elucidate the relationships of β-glucan receptor dectin-1 (D1) and α-mannan receptor dectin-2 (D2) to the onset of that vasculitis. The incidence and histological severity of vasculitis were compared among mice lacking the genes for D1 or D2 (i.e.

[Preparation and Biological Characterization of Limulus Factor G-activating Substance of Aspergillus spp.].

Aspergillus is a medically important fungal genus that causes a life-threatening infection known as aspergillosis in immunocompromised patients. β-1,3-Glucan is detected in the plasma of patients with aspergillosis and appears to be useful for the diagnosis of aspergillosis. In this study, we cultured Aspergillus spp.

Non-receptor type, proline-rich protein tyrosine kinase 2 (Pyk2) is a possible therapeutic target for Kawasaki disease.

Kawasaki disease (KD) is a paediatric vasculitis whose pathogenesis remains unclear. Based on experimental studies using a mouse model for KD, we report here that proline-rich protein tyrosine kinase 2 (Pyk2) plays a critical role in the onset of KD-like murine vasculitis. The mouse model for KD was prepared by administrating a Candida albicans water-soluble fraction (CAWS).

A sphingosine 1-phosphate receptor agonist ameliorates animal model of vasculitis.

Objectives: Sphingosine 1-phosphate (S1P) is a bioactive lipid that binds to cell surface receptors (S1P). In this study, we examined the effect of S1P agonist, ONO-W061, on murine Candida albicans water-soluble fraction (CAWS)-induced vasculitis.

Methods: Mice were administered ONO-W061, and the number of peripheral blood cells was counted.

Genetic Phagocyte NADPH Oxidase Deficiency Enhances Nonviable Candida albicans-Induced Inflammation in Mouse Lungs.

Patients with chronic granulomatous disease (CGD) have mutated phagocyte NADPH oxidase, resulting in reduced production of reactive oxygen species (ROS). While the mechanism underlying hyperinfection in CGD is well understood, the basis for inflammatory disorders that arise in the absence of evident infection has not been fully explained. This study aimed to evaluate the effect of phagocyte NADPH oxidase deficiency on lung inflammation induced by nonviable Candida albicans (nCA).

Immunochemical Cross-Reactivity of β-Glucan in the Medicinal Plant, Sasa veitchii (Japanese Folk Medicine Kumazasa), and Medicinal Mushrooms.

Fungal β-glucan is a representative pathogen-associated molecular pattern from mushroom, yeast, and fungi and stimulates innate as well as acquired immune systems. This β-glucan is widely applied in functional food to enhance immunity. Humans and animals generally become sensitized to this β-glucan and gradually produce specific antibodies to β-glucans.

Specificity of the Immunomodulating Activity of Sasa veitchii (Japanese Folk Medicine Kumazasa) to Fungal Polysaccharides.

Many plant extracts are used as well-known folk medicines and exhibit various biological activities that are beneficial to human health. These extracts contain polysaccharides, and some are pathogen-associated molecular patterns (PAMPs) that stimulate innate as well as acquired immune systems. In the present study, the cooperative effects of PAMPs and bamboo water-soluble methanol precipitation (BWMP) in a macromolecular fraction of the hot water extract of Sasa veitchii (in Japanese folk medicine, known as Kumazasa; family Poaceae) were analyzed in vitro using the spleen or bone marrow cells of mice.

Involvement of mannose-binding lectin in the pathogenesis of Kawasaki disease-like murine vasculitis.

Kawasaki disease (KD) is a paediatric idiopathic vasculitis. In this study, on the basis of studies using an established animal model for KD, we report that mannose-binding lectin (MBL) is involved in the pathogenesis of the disease. KD-like experimental murine vasculitis was induced by intraperitoneally administering a Candida albicans water-soluble extract (CAWS).

Oral administration of soluble β-glucan preparation from the cauliflower mushroom, Sparassis crispa (Higher Basidiomycetes) modulated cytokine production in mice.

Soluble β-glucan preparation from the cold NaOH extract of Sparassis crispa (SCG) is a six-branched 1,3-β-D-glucan that is a major cell-wall structural component in fungi. Leukocytes from DBA/2 mice are highly sensitive to SCG, producing cytokines in vitro. We previously reported that the intraperitoneal (i.

The role of TNF-α in a murine model of Kawasaki disease arteritis induced with a Candida albicans cell wall polysaccharide.

Objectives: Various inflammatory cytokines, including tumor necrosis factor-α (TNF-α), have been reported to play roles in Kawasaki disease (KD). Recently, anti-TNF-α therapy was reported to show efficacy in patients who do not respond to high-dose intravenous immunoglobulin therapy. However, there are many gaps in our understanding of the role that TNF-α plays in the development of KD arteritis as well as whether anti-TNF-α therapy causes any histological changes in the arteritis.

Modulation of interferon-γ synthesis by the effects of lignin-like enzymatically polymerized polyphenols on antigen-presenting cell activation and the subsequent cell-to-cell interactions.

Lignin-like polymerized polyphenols strongly activate lymphocytes and induce cytokine synthesis. We aimed to characterise the mechanisms of action of polymerized polyphenols on immunomodulating functions. We compared the reactivity of leukocytes from various organs to that of polymerized polyphenols.

Myeloperoxidase deficiency in mice exacerbates lung inflammation induced by nonviable Candida albicans.

Objective: This study aimed to evaluate the effect of myeloperoxidase (MPO) deficiency on lung inflammation induced by nonviable Candida albicans (nCA).

Methods: Mice were inoculated intranasally with nCA, and accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid was analyzed by flow cytometry. The levels of macrophage inflammatory protein 2 (MIP-2), keratinocyte-derived chemokine (KC), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in the lung were measured by ELISA.

Analysis of the titer and reactivity of antibody/ies against fungal cell wall β-glucans in human sera.

The aim of this work was to characterize an antibody response to β-glucan (BG), a major component of the fungal cell wall, at each isotype in human sera. The titer and reactivity of the anti-human BG antibody were examined using enzyme-linked immunosorbant assay plates coated with Candida soluble cell wall β-glucan as a standard antigen. The antibody was detected using anti-human immunoglobulin (Ig) G, IgM, and IgA.

Am80, a retinoic acid receptor agonist, ameliorates murine vasculitis through the suppression of neutrophil migration and activation.

Objective: Vasculitis is characterized by leukocyte infiltration in the vessel walls, with destructive damage to mural structures. Retinoids are compounds that bind to retinoic acid receptors and exert biologic activities similar to those of vitamin A, including modulatory effects on cell proliferation and differentiation. This study was undertaken to examine the therapeutic effects of a synthetic retinoid, Am80, in a murine model of vasculitis induced by Candida albicans water-soluble fraction (CAWS).

Important role of CCR2 in a murine model of coronary vasculitis.

Background: Chemokines and their receptors play a role in the innate immune response as well as in the disruption of the balance between pro-inflammatory Th17 cells and regulatory T cells (Treg), underlying the pathogenesis of coronary vasculitis in Kawasaki disease (KD).

Results: Here we show that genetic inactivation of chemokine receptor (CCR)-2 is protective against the induction of aortic and coronary vasculitis following injection of Candida albicans water-soluble cell wall extracts (CAWS). Mechanistically, both T and B cells were required for the induction of vasculitis, a role that was directly modulated by CCR2.

[Role of neutrophil-derived reactive oxygen species in host defense and inflammation].

Neutrophil accumulation is a critical event in the pathogenesis of inflammation. The generation of hypochlorous acid by myeloperoxidase (MPO) in neutrophils is crucial to the host defense response. MPO-deficient (MPO-KO) mice showed severely reduced cytotoxicity to Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans and other microorganisms, demonstrating that an MPO-dependent oxidative system is important for in vivo host defense against fungi.