vWA proteins of Leptospira interrogans induce hemorrhage in leptospirosis by competitive inhibition of vWF/GPIb-mediated platelet aggregation
Authors: Muhammad Imran
Yang Li
Jie Yan
Wei-Lin Hu
David M Ojcius
Xu&#x27;ai Lin
Jia-Qi Fang
Kai-Xuan Li
Yu-Mei Ge
Journal: EBioMedicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: Competitive inhibition; Hemorrhage; Leptospira interrogans; Leptospirosis; Platelet aggregation
Affiliations: Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, PR China., Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, PR China. Electronic address: ., Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, PR China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China., Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, 155 Fifth Street, San Francisco, CA 94103, USA. Electronic address: ., Center of Clinical Laboratory Medicine, the People's Hospital of Zhejiang Province, Zhejiang 310014, PR China., Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, PR China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China. Electronic address: .

Abstract:  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 aggregation and its signaling kinases and active components were detected by lumiaggregometry, Western analysis, spectrophotometry and confocal microscopy. Hu-GPIbα-binding sites in rLep-vWA-I and rLep-vWA-II were identified by SPR/ITC measurements. Findings: Both rLep-vWA-I and rLep-vWA-II were able to bind to Hu-platelets and inhibit rHu-vWF/ristocetin-induced Hu-platelet aggregation, but Hu-GPIbα-IgG, rLep-vWA-I-IgG and rLep-vWA-II-IgG blocked this binding or inhibition. SPR and ITC revealed a tight interaction between Hu-GPIbα and rLep-vWA-I/rLep-vWA-II with KD values of 3.87 × 10-7-8.65 × 10-8 M. Hu-GPIbα-binding of rL-vWA-I/rL-vWA-II neither activated the PI3K/AKT-ERK and PLC/PKC kinases nor affected the NO, cGMP, ADP, Ca2+ and TXA2 levels in Hu-platelets. G13/R36/G47 in Lep-vWA-I and G76/Q126 in Lep-vWA-II were confirmed as the Hu-GPIbα-binding sites. Injection of rLep-vWA-I or rLep-vWA-II in mice resulted in diffuse pulmonary and focal renal hemorrhage but this hemorrhage was blocked by rLep-vWA-I-IgG or rLep-vWA-II-IgG. Interpretation: The products of L. interrogans vwa-I and vwa-II genes induce hemorrhage by competitive inhibition of vWF-mediated Hu-platelet aggregation. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. In this paper, the absorption of CO and CO2 molecules on borophene without or with lithium is studied. Let s call this paper  SNAS 2020 . Figures and table values of this paper, published in June 2020, look remarkably similar to those in another paper by the same group of authors, i.e. Arefi et al., Computational and Theoretical Chemistry 1197 (2021) 113159, doi: 10.1016 j.comptc.2021.113159. Let s call that paper  CTC 2021 . In the CTC 2021 paper, the absorption of CO and CO2 molecules on borophene without or with sodium is studied. Here are some comparisons between the two papers. SNAS 2020 (this paper) will be shown on the left, and the CTC 2021 paper on the right. Titles and abstract look different, there are no concerns about textual reuse. ![file] Here are Figures 1 from both papers. One could argue that these are just diagrams. ![file] Tables 1 from both papers show remarkably similar values. ![file] Figures 5 from both papers show remarkably similar plots. Note that one of the  band structure plots is stretched differently and that the  density of states (DOS) plots are in mirror image, respectively. ![file] Figures 8 from both papers also show remarkably similar plots, even though SNAS 2020 s figures show plot obtained with lithium, and the CTC 2021 with sodium. Note that the  density of states (DOS) plots are in mirror image and, in one occasion, stretched differently. ![file] Figures 10 from both papers might also look similar, although they are arranged differently. ![file] ,