Dentistry Commons^™

Vwa Proteins Of Leptospira Interrogans Induce Hemorrhage In Leptospirosis By Competitive Inhibition Of Vwf/Gpib-Mediated Platelet Aggregation., Jia-Qi Fang, Muhammad Imran, Wei-Lin Hu, David M. Ojcius, Yang Li, Yu-Mei Ge, Kai-Xuan Li, Xu'ai Lin, Jie Yan

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BACKGROUD: Leptospira interrogans is the major causative agent of leptospirosis, a worldwide zoonotic disease. Hemorrhage is a typical pathological feature of leptospirosis. Binding of von Willebrand factor (vWF) to platelet glycoprotein-Ibα (GPIbα) is a crucial step in initiation of platelet aggregation. The products of L. interrogans vwa-I and vwa-II genes contain vWF-A domains, but their ability to induce hemorrhage has not been determined.

METHODS: Human (Hu)-platelet- and Hu-GPIbα-binding abilities of the recombinant proteins expressed by L. interrogans strain Lai vwa-I and vwa-II genes (rLep-vWA-I and rLep-vWA-II) were detected by flowcytometry, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Hu-platelet …

A Novel Fas-Binding Outer Membrane Protein And Lipopolysaccharide Of Leptospira Interrogans Induce Macrophage Apoptosis Through The Fas/Fasl-Caspase-8/-3 Pathway., Peng Du, Shi-Jun Li, David M. Ojcius, Kai-Xuan Li, Wei-Lin Hu, Xu'ai Lin, Ai-Hua Sun, Jie Yan

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Leptospira interrogans is the major causative agent of leptospirosis, an emerging, globally spreading zoonotic infectious disease. The pathogen induces macrophage apoptosis, but the molecular basis and mechanism remain unknown. In the present study, we found that L. interrogans caused apoptosis of phagocytosis-inhibited macrophages, and the product of the L. interrogans LB047 gene (Lep-OMP047) was the unique protein captured by mouse and human Fas proteins. The recombinant expressed Lep-OMP047 (rLep-OMP047) strongly bound mouse and human Fas proteins with equilibrium association constant (K

Bid-Induced Release Of Aif/Endog From Mitochondria Causes Apoptosis Of Macrophages During Infection With, Wei-Lin Hu, Hai-Yan Dong, Yang Li, David M. Ojcius, Shi-Jun Li, Jie Yan

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Leptospirosis is a global zoonotic infectious disease caused by pathogenic Leptospira species. Leptospire-induced macrophage apoptosis through the Fas/FasL-caspase-8/3 pathway plays an important role in the survival and proliferation of the pathogen in hosts. Although, the release of mitochondrial apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in leptospire-infected macrophages has been described, the mechanisms linking caspase and mitochondrion-related host-cell apoptosis has not been determined. Here, we demonstrated that leptospire-infection induced apoptosis through mitochondrial damages in macrophages. Apoptosis was caused by the mitochondrial release and nuclear translocation of AIF and/or EndoG, leading to nuclear DNA fragmentation. However, the mitochondrion-related CytC-caspase-9/3 pathway was …

Mononuclear-Macrophages But Not Neutrophils Act As Major Infiltrating Anti-Leptospiral Phagocytes During Leptospirosis., Xu Chen, Shi-Jun Li, David M. Ojcius, Ai-Hua Sun, Wei-Lin Hu, Xu'ai Lin, Jie Yan

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OBJECTIVE: To identify the major infiltrating phagocytes during leptospirosis and examine the killing mechanism used by the host to eliminate Leptospira interrogans.

METHODS: Major infiltrating phagocytes in Leptospira-infected C3H/HeJ mice were detected by immunohistochemistry. Chemokines and vascular endothelial cell adhesion molecules (VECAMs) of Leptospira-infected mice and leptospirosis patients were detected by microarray and immunohistochemistry. Leptospira-phagocytosing and -killing abilities of human or mouse macrophages and neutrophils, and the roles of intracellular ROS, NO and [Ca2+]i in Leptospira-killing process were evaluated by confocal microscopy and spectrofluorimetry.

RESULTS: Peripheral blood mononuclear-macrophages rather than neutrophils were the main infiltrating phagocytes in the lungs, liver …