Dapsone suppresses human neutrophil superoxide production and elastase release in a calcium-dependent manner
T. Suda
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorY. Suzuki
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorT. Matsui
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorT. Inoue
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorO. Niide
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorT. Yoshimaru
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorH. Suzuki
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorC. Ra
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorT. Ochiai
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorT. Suda
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorY. Suzuki
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorT. Matsui
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorT. Inoue
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorO. Niide
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorT. Yoshimaru
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorH. Suzuki
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorC. Ra
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorT. Ochiai
Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan *Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Centre, Nihon University Graduate School of Medical Sciences, Tokyo, Japan
Search for more papers by this authorConflicts of interest: none declared.
Summary
Background Dapsone (4,4′-diaminodiphenyl sulphone) is a powerful therapeutic tool in many skin diseases including neutrophilic dermatoses. The drug has an outstanding therapeutic efficacy against many skin diseases characterized by neutrophil-rich infiltrates; however, mechanisms of its action are poorly understood.
Objectives We investigated the effects of dapsone on respiratory and secretory functions of human neutrophils triggered by the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), the physiological agonist C5a, and phorbol myristate acetate (PMA).
Methods Human neutrophils were isolated from venous blood obtained from healthy donors. We detected extracellular production of superoxide (O2–) by cytochrome C reduction assay, and intracellular production of O2– by flow cytometry. Neutrophil elastase release was measured by the cleavage of the specific elastase substrate N-methoxysuccinyl-Ala-Ala-Pro-Val-p-nitroanilide. Measurement of cytosolic free calcium concentration was performed using the calcium-reactive fluorescence probe, Fluo-3.
Results Dapsone suppressed intra- and extracellular production of O2– and elastase release triggered by fMLP and C5a, but not by PMA. Both fMLP and C5a signalled the above pathways by inducing calcium influx, but PMA functions bypassed calcium influx. Dapsone was capable of antagonizing the induction of calcium influx.
Conclusions These findings suggest that one mechanism of the anti-inflammatory action of dapsone is inhibition of calcium-dependent functions of neutrophils including release of tissue-damaging oxidants and proteases in the affected skin.
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