title: Pulmonary platelet accumulation induced by catecholamines: Its involvement in lipopolysaccharide-induced anaphylaxis-like shock.
abstract: Intravenously injected lipopolysaccharides (LPS) rapidly induce pulmonary platelet accumulation (PPA) and anaphylaxis-like shock (ALS) in mice. Macrophages reportedly release catecholamines rapidly upon stimulation with LPS. Here, we examined the involvement of macrophage-derived catecholamines in LPS-induced PPA and ALS. A catecholamine or Klebsiella O3 (KO3) LPS was intravenously injected into mice, with 5-hydroxytryptamine in the lung being measured as a platelet marker. The tested catecholamines induced PPA, leading to shock. Their minimum shock-inducing doses were at the nmol/kg level. The effects of epinephrine and norepinephrine were inhibited by prazosin (α1 antagonist) and by yohimbine (α2 antagonist), while dopamine's were inhibited only by prazosin. Use of synthetic adrenergic α1- and/or α2-agonists, platelet- or macrophage-depleted mice, a complement C5 inhibitor and C5-deficient mice revealed that (a) α2-receptor-mediated PPA and shock depend on both macrophages and complements, while α1-receptor-mediated PPA and shock depend on neither macrophages nor complements, (b) the PPA and ALS induced by KO3-LPS depend on α1- and α2-receptors, macrophages, and complements, and (c) KO3-LPS-induced PPA is preceded by catecholamines decreasing in serum. Together, these results suggest the following. (i) Catecholamines may stimulate macrophages and release complement C5 via α2-receptors. (ii) Macrophage-derived catecholamines may mediate LPS-induced PPA and ALS. (iii) Moderate PPA may serve as a defense mechanism to remove excess catecholamines from the circulation by promoting their rapid uptake, thus preventing excessive systemic effects. (iv) The present findings might provide an insight into possible future pharmacological strategies against such diseases as shock and acute respiratory distress syndrome.
authors.affiliation: Division of Molecular Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Department of Disaster Psychiatry, International Research Institute for Disaster Science, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. Electronic address: yu_zhiqian@med.tohoku.ac.jp.
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Science, Aomori University, 2-3-1 Koubata, Aomori 030-0943, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Hirotada
authors.initials: H
authors.lastname: Otsuka
authors.affiliation: Division of Molecular Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shikama
authors.affiliation: Division of Molecular Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Division of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Department of Pediatric Dentistry, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Funayama
authors.affiliation: Department of Disaster Psychiatry, International Research Institute for Disaster Science, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Sakai
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Science, Aomori University, 2-3-1 Koubata, Aomori 030-0943, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murai
authors.affiliation: Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University, Nagakute, Aichi 48-1955, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
authors.affiliation: Division of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Takada
authors.affiliation: Division of Molecular Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: Division of Molecular Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Endo
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002395:Catecholamines / Q000494:pharmacology*; D002478:Cells, Cultured; D003182:Complement C5 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011224:Prazosin / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D012701:Serotonin / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D003182:Complement C5; D008070:Lipopolysaccharides; D015016:Yohimbine; D012701:Serotonin; D011224:Prazosin
keywords: 5-Hydroxytryptamine; Anaphylaxis-like lethal shock; Catecholamine; Complement C5; Macrophage; Pulmonary platelet accumulation