Kohei Honda

Akita University Hospital, Akita, Akita, Japan

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Publications (11)45.61 Total impact

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    ABSTRACT: It is assumed that the very late antigen-4 (VLA-4) plays a key role in selective migration and accumulation of eosinophils to the allergic inflammatory focus. The regulatory mechanism for VLA-4 expression is poorly understood, as is its relationship between other adhesion molecules. The aim of the study was to elucidate the relationship between VLA-4 expression and the activation of eosinophils. The surface expression of VLA-4, Mac-1, ICAM-1, CD4, CD25, CD69, CD89, IL-5 receptor and GM-CSF receptor on eosinophils isolated from the peripheral blood of 15 patients with eosinophilia and 16 healthy volunteers was measured. The surface expression of VLA-4 presented in mean fluorescent intensity by flow-cytometric analysis showed a significant decrease in the patients with eosinophilia (>700 eosinophils/microl) compared to that of the subjects without eosinophilia. On the other hand, the surface expression of Mac-1 was significantly increased in the patients with eosinophilia. There was an inverse correlation between the expression of VLA-4 and that of Mac-1 (r = -0.81) on the eosinophils obtained from the patients with eosinophilia. The changes on the surface expressions of Mac-1 and VLA-4 may be indicating the activation of eosinophils in the patients with eosinophilia and may contribute to their migration to the allergic inflammatory focus.
    No preview · Article · Jun 2001 · International Archives of Allergy and Immunology
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    ABSTRACT: The CC chemokine eotaxin not only attracts eosinophils to inflamed sites but also promotes adhesion, degranulation and reactive oxygen species production of eosinophils. Reactive oxygen species released from eosinophils are believed to injure epithelial cells at inflamed sites, resulting in airway hyperresponsiveness. Roxithromycin has been reported to have antiasthmatic effects, although its mechanism of action is not thoroughly understood. Therefore, the effect of roxithromycin on eotaxin-primed reactive oxygen species production from eosinophils was studied. Reactive oxygen species production by eosinophils cultured with or without roxithromycin was evaluated using luminol-dependent chemiluminescence. Roxithromycin inhibited the release of reactive oxygen species from eosinophils evoked with the calcium ionophore A23187, regardless of pretreatment with or without eotaxin. Roxithromycin may protect epithelial cells at inflamed sites, at least partly by inhibiting the release of reactive oxygen species from eosinophils.
    No preview · Article · Feb 2001 · International Archives of Allergy and Immunology
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    ABSTRACT: Graft-versus-host disease is one of the major complications after allogenic bone marrow transplantation, but it is not easy to anticipate the onset. The purpose of this study was to determine clinically useful markers of acute graft-versus-host disease. We measured the serum levels of tumor necrosis factor-alpha, soluble tumor necrosis factor receptor 1, soluble c-kit, soluble Fas, soluble intercellular adhesion molecule-1, growth-related oncogene protein-alpha, thrombomodurin, and interleukin-16 in 13 patients at 1 to 7 weeks after allogenic bone marrow transplantation. The patients with acute graft-versus-host disease showed a significant increase of tumor necrosis factor, soluble tumor necrosis factor receptor 1, soluble Fas, soluble intercellular adhesion molecule-1, and growth-related oncogene protein-alpha, although there was a decrease of soluble c-kit. The increases of serum soluble tumor necrosis factor receptor 1, intercellular adhesion molecule-1, and growth-related oncogene protein-alpha were preceded by the elevation of soluble Fas. The patients with acute graft-versus-host disease had increased serum levels of tumor necrosis factor-alpha, soluble tumor necrosis factor receptor 1, soluble Fas, and soluble intercellular adhesion molecule 1 and a decreased soluble c-kit level. Tumor necrosis factor-alpha and soluble c-kit were shown to be sensitive and specific parameters for graft-versus-host disease after bone marrow transplantation, and soluble Fas was shown to be a predictor of acute graft-versus-host disease after bone marrow transplantation.
    No preview · Article · Aug 2000 · Journal of Allergy and Clinical Immunology
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    ABSTRACT: Background: Recently, adhesion molecules have been suggested to play an important role in allergic inflammatory diseases such as bronchial asthma. It is unclear whether eosinophil activation and paracrine or autocrine synthesis of eosinophilopoietic growth cytokines is mediated through signaling by intercellular adhesion molecule-1 (ICAM-1) and the β2 integrin family. Objective: We examined whether signaling by ICAM-1 and its ligands (β2 integrins) could prolong eosinophil survival. Methods: Eosinophils were isolated from patients with hypereosinophilia by modified CD16 negative selection. After culture with or without recombinant soluble ICAM-1, eosinophil viability was measured by trypan blue dye exclusion. Results: Eosinophil survival was prolonged in cultures with recombinant soluble ICAM-1 compared with cultures without it (P
    No preview · Article · Jul 2000 · Journal of Allergy and Clinical Immunology
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    ABSTRACT: It is known that growth hormones such as insulin-like growth factor-I (IGF-I) and several kinds of cytokines are involved in the regeneration process of injured epithelial cells in chronic respiratory inflammatory diseases such as bronchial asthma. Repetitive degeneration/regeneration processes of the airway epithelial layer is supposed to be responsible for the remodeling and irreversible organic changes of the airway in bronchial asthma. The purpose of this study is to establish a simple and reliable in vitro method for studying airway epithelial cell growth and proliferation using IGF-I. By altering the number of cultured epithelial cells (strain NCI-H(292)), culture duration before stimulation with IGF-I, concentration of IGF-I, and duration of IGF-I stimulation, the optimum conditions for epithelial cell growth was determined. The epithelial cell growth was evaluated using [methyl-(3)H]thymidine uptake. Among various culture conditions, the epithelial cells cultured at 1 x 10(3) cells/well for 24 h followed by 24 h of stimulation by 10(-8) M of IGF-I showed the highest growth. The method for the evaluation of epithelial cell growth established in this study requires a small number of cells and has no complicated procedure. This simple model enables us to investigate the effect of various substances on bronchial epithelial cell growth in the presence of IGF-I.
    No preview · Article · Jun 2000 · International Archives of Allergy and Immunology
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    ABSTRACT: The early detection of retroperitoneal masses in children, such as neuroblastoma, Wilm's tumor, hydronephrosis and cystic renal diseases, has a great clinical importance for the improvement of their prognosis. The kidney is often affected in its size or position by these lesions, and occasionally allows clinicians to find a clue to reach the correct diagnosis before the patient become symptomatic. Since we had no clinically available nomogram on the position and the size of the kidney in Japanese children, we measured the size and position of the kidneys on plain abdominal x-rays in 347 Japanese children in preschool years with a special attention to their relationship with the spine. As a result, the nomogram showed age dependent growth of the kidneys keeping almost the same ratio with the spine, while the distance between the upper pole of the kidney and the spine remained less than 10 mm in all age groups. Our nomogram may be useful not only for picking up the malposition of the kidneys but also for the follow up of the patients with chronic renal diseases affecting the growth of the kidneys.
    Preview · Article · Jun 1999 · The Tohoku Journal of Experimental Medicine
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    ABSTRACT: The CC chemokine eotaxin is a selective chemoattractant for eosinophils. Eosinophils have been considered to be the major effector cells in allergic inflammation, since not only eosinophil-specific granule proteins but also reactive oxygen species (ROS) from eosinophils may cause the damage to the cells or tissue of the mucosal epithelium. In this study, we examined the effect of eotaxin on ROS from an eosinophil cell line, YY-1. ROS in luminol-dependent reaction were examined. Calcium ionophore A23187 were added to the mixture of YY-1 cells with luminol, and then ROS were determined. Eotaxin primed the production of ROS from YY-1 cells. ROS from untreated YY-1 cells evoked with calcium ionophore A23187 in luminol-dependent chemiluminescence gave a maximal value of 1,928 +/- 223 intensity counts (IC; mean +/- SE, n = 4) and an integral value of 17.04 +/- 1. 51 IC (x10(-4)), while eosinophils that were treated with eotaxin gave a maximal value of 2,264 +/- 86 IC (10 nM), 2,691 +/- 124 IC (100 nM) and an integral value of 21.22 +/- 0.67 IC (x10(-4); 10 nM), 26.20 +/- 1.41 IC (x10(-4); 100 nM). Eotaxin might play important roles in the pathogenesis of allergic inflammation through eosinophil activation by priming of eosinophil oxidative metabolism as well as involvement in selective eosinophil chemotaxis.
    No preview · Article · Feb 1999 · International Archives of Allergy and Immunology
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    ABSTRACT: RANTES and eotaxin are important chemokines involved in the activation and migration of eosinophils and are considered to play a major role in allergic inflammation. In this study, we used RT-PCR to investigate the kinds of cells that express mRNA for CCR3, a common receptor of these chemokines, and eotaxin, a ligand for CCR3. CCR3 mRNA was expressed in eosinophils, peripheral mononuclear cells, an eosinophilic cell line (EoL-1), a bronchial epithelial cell line (NCI-H(292)), human endothelial cells and nasal washings from patients with allergic rhinitis. These results suggest that the CCR3-eotaxin system plays an important role in generating inflammation, since these substances are expressed not only in cells implicated in activation or migration of eosinophils but also in various other cells involved in allergic inflammation.
    No preview · Article · Feb 1999 · International Archives of Allergy and Immunology
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    ABSTRACT: Activation of eosinophils is closely associated with the pathology of allergic inflammatory disease, especially bronchial asthma. We recently investigated the activation of eosinophils by applying whole blood to a flow cytometer. We measured here beta1 and beta2 integrin on eosinophils stimulated by phorbol-12-myristate-13-acetate (PMA)/ionomycin to evaluate eosinophil activation in vitro using whole blood. Heparinized whole blood was diluted with the same volume of RPMI 1640, then cells were incubated in the presence or absence of PMA and ionomycin for 45 min at 37 degrees C. After hemolyzation with lysing solution, flow-cytometric findings for CR3, LFA1-alpha, LFA1-beta and VLA-4 expression on eosinophils were examined. Mean fluorescent intensity (MFI) of CR3 and LFA1-beta stimulated by PMA and ionomycin was significantly higher than that of the unstimulated control. MFI of LFA1-alpha showed no significant difference from the unstimulated control. On the other hand, MFI of VLA-4 tended to decrease. Our method to distinguish eosinophils from various cell groups in whole blood is simple and time-saving, similar to conditions in vivo and may allow intensive investigation of eosinophils in clinical laboratories as well as in research laboratories. We are currently investigating the influence of different kinds of stimulations, regulation factors or agents on eosinophils using this method.
    No preview · Article · Feb 1999 · International Archives of Allergy and Immunology

  • No preview · Article · Nov 1998 · Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology
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    ABSTRACT: RANTES (regulated on activation, normal T expressed and secreted) has been shown to possess chemotactic activity for eosinophils. Eosinophils have been considered to play a key role in the allergic inflammation through the release of inflammatory molecules such as radical oxygen products. Thus, in this study, we examined the effect of RANTES on radical oxygen products from eosinophils. Eosinophils were isolated from heparinized venous blood of patients with bronchial asthma by the modified CD16-negative depletion method. Radical oxygen products were examined in terms of lucigenin-dependent chemiluminescence. To a mixture of 50 microl of eosinophils (2x10(6)/ml) and 50 microl of lucigenin (5x10(-4)M), 50 microl of calcium ionophore A23187 (final concentration 10(-5)M) was added, and radical oxygen products were determined for 600 s. RANTES treatment resulted in the enhancement of peak value (0.64+/-0.23 RLU) and integrated value (119.08+/-20.52 RLU) as compared to untreated cells (0.15+/-0.03 RLU, 29.48+/-8.92 RLU, respectively). CONCLUSIONS We could conclude that RANTES might play an important role in the pathogenesis of allergic inflammation through involvement in selective eosinophil infiltration and eosinophil activation by augmentation of eosinophil oxidative metabolism.
    No preview · Article · Oct 1998 · International Archives of Allergy and Immunology