Binding to complement factors and activation of the alternative pathway by Acanthamoeba |
| |
| Authors: | Wilawan Pumidonming Julia Walochnik Elke Dauber Franz Petry |
| |
| Affiliation: | 1. Department of Medical Parasitology, Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Kinderspitalgasse 15, 1090 Vienna, Austria;2. Institute of Medical Microbiology and Hygiene, University Medical Center of the Johannes Gutenberg University Mainz, Augustusplatz/Hochhaus, D-55101 Mainz, Germany;1. Institute for Transfusion Medicine and Immune Hematology, German Red Cross Blood Donor Service Baden-Wuerttemberg–Hessen, Clinics of the Johann Wolfgang Goethe University, Hessen, Germany;;2. Children''s Hospital of Philadelphia, Philadelphia, PA;;3. Hemophilia Center Frankfurt, Clinics of the Johann Wolfgang Goethe University, Hessen, Germany;;4. Institute for Biomedical Research Georg-Speyer-Haus, Frankfurt, Germany;3. From the Division of Pharmacology and Toxicology, College of Pharmacy, Institute for Cellular and Molecular Biology, and Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712 and;4. the Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461;1. Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil;2. Interdisciplinary Center for Gene Therapy, Federal University of São Paulo, São Paulo, Brazil;3. Department of Pharmacology, University of Oxford, Oxford, UK;4. Department of Cell and Developmental Biology, University College London, London, UK;1. Military Veterinary Institute, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun 130122, Jilin Province, China;2. College of Life Science, Jilin Agricultural University, 2888 Xincheng Street, Changchun 130118, Jilin Province, China;1. Chinese Academy of Agricultural Sciences, Shanghai Veterinary Research Institute, CAAS, 518 Ziyue Road, Minhang, Shanghai 200241, PR China;2. College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China |
| |
| Abstract: | Acanthamoeba can cause severe ocular and cerebral diseases in healthy and immunocompromised individuals, respectively. Activation of complement appears to play an important role in host defence against infection. The exact mechanism, however, is still unclear. The aim of the present study was to investigate the effect of normal human serum (NHS) and normal mouse serum (NMS) on Acanthamoeba trophozoites, the binding of different complement factors to Acanthamoeba and the activation of the complement system. Moreover, we aimed to work out any possible differences between different strains of Acanthamoeba. A virulent T4 strain, a non-virulent T4 strain and a virulent T6 strain were included in the study. It was shown that NHS, but not NMS clearly has amoebicidal properties. After 5 min of incubation with NHS, amoebae showed plasma membrane disruption and extrusion of intracellular components. Cells were completely destroyed within 60 min of incubation in NHS but stayed intact after incubation in heat-inactivated serum. The binding of human C3 and C9 to amoebae was established by immunoblotting. Although incubation with mouse serum did not result in lysis of Acanthamoeba trophozoites an immunofluorescence assay (IFA) demonstrated a strong deposition of mouse complement factor C3 activation products, moderate binding of C1q, but no binding of MBL-A and MBL-C. EDTA inhibited the binding of C3 to acanthamoebae. Binding of amoebae to C3b was observed with sera from C1qa?/? and MBL-A/C?/? mice, but not with serum from Bf/C2?/? mice demonstrating an activation of complement via the alternative pathway. There were no significant differences between the three Acanthamoeba strains investigated. Altogether, our results prove that NHS is amoebolytic and that Acanthamoeba binds to C3 and C9 and activates the complement system via the alternative pathway. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
