Nitric oxide mediates distinct effects of various LPS chemotypes on phagocytosis and leukotriene synthesis in human neutrophils |
| |
| Authors: | Anna N Zagryazhskaya Sabine C Lindner Zoryana V Grishina Svetlana I Galkina Dieter Steinhilber Galina F Sud’ina |
| |
| Institution: | 1. A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Leninskie Gory, Moscow 119991, Russia;2. Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University Frankfurt, 60438 Frankfurt am Main, Germany;1. Division of Tuberculosis Elimination, The National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention, Atlanta, GA 30329, USA;1. The Department of Otorhinolaryngology, Head and Neck Surgery of Kitasato University Hospital, Kanagawa, Japan;2. The Department of Otorhinolaryngology of National Hospital Organization Sagamihara National Hospital, Kanagawa, Japan;3. The Clinical Research Center, National Hospital Organization Sagamihara National Hospital, Kanagawa, Japan;4. The Third Department of Internal Medicine, Kagoshima University School of Medicine, Kagoshima, Japan;1. Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina;2. Departamento de Patología, Centro de Estudios Oncológicos, Academia Nacional de Medicina, Buenos Aires, Argentina;3. Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina;1. Russian Cardiology Research and Production Center, 3rd Cherepkovskaya Street, 15A, Moscow 121552, Russia;2. Research Institute of Physico-Chemical Medicine, Malaya Pirogovskaya Street, 1a, Moscow 119992, Russia;1. Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, 3460000 Talca, Chile;2. Laboratorio de Productos Naturales, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1, Chile;3. Unidad de Pruebas Biológicas, Instituto de Salud Pública de Chile, Marathon 1000, Santiago, Chile;4. Universidad Científica del Peru. Avda. Abelardo Quiñones Km 2.5, Iquitos, Peru;5. Instituto de Biotecnología, Facultad de Ingeniería, Universidad Nacional de San Juan, Av. Libertador General San Martin 1109 (oeste), CP 5400, San Juan, Argentina |
| |
| Abstract: | We investigated the effect of lipopolysaccharide (LPS) chemotypes differing in their carbohydrate chain length on phagocytosis of serum-opsonized zymosan (OZ) particles and related functions of human polymorphonuclear leukocyte (PMNL, neutrophils). LPS from deep core mutant (Re), complete core (Ra) and smooth (S) phenotypes of Salmonella typhimurium was studied. Priming of neutrophils with various LPSs caused prominent enhancement of OZ phagocytosis, superoxide production and leukotriene (LT) synthesis in neutrophils, with LPS effects increasing as Re < S < Ra. The LPS forms were less potent to activate OZ uptake in the presence of MK-886, 5-lipoxygenase activating protein inhibitor, suggesting the regulatory function of 5-lipoxygenase (5-LO)-derived LTs. Direct measurement of nitrite release from OZ-stimulated neutrophils revealed that the effects of LPS on NO synthesis increased in the range of Ra < S < Re. Nitric oxide synthase (NOS) inhibitor l-NAME increased phagocytosis, LT and superoxide formation by neutrophils, and abolished the difference in the action of the LPSs forms. Further mechanistic studies revealed that NO modulates cellular 5-LO activity in a guanylyl cyclase and protein kinase G dependent manner, as well as interplay between NO and superoxide, and peroxynitrite generation contribute to distinct effects of LPS chemotypes on phagocytosis and LT synthesis in human neutrophils. Our investigation of the three LPS species demonstrates that the LPS polysaccharide core is mostly essential for the PMNL activation and is able to suppress lipid A-induced increase in NOS activity in phagocyting cells by triggering specific signaling cascades. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
