A novel leptospiral protein increases ICAM-1 and E-selectin expression in human umbilical vein endothelial cells

Abstract

It has been reported previously that activation of vascular endothelium by outer membrane proteins of the spirochetes Borrelia sp. and Treponema sp. resulted in enhanced expression of endothelial cell adhesion molecules. To investigate the role of leptospiral proteins in this process, a predicted lipoprotein encoded by the gene LIC10365 was selected, which belongs to a paralogous family that presents a domain of unknown function, DUF1565. The LIC10365 gene was cloned and the protein expressed in Escherichia coli C43 (DE3) strain using the vector pAE. The recombinant protein tagged with N-terminal hexahistidine was purified by metal-charged chromatography and was used to assess its ability to activate cultured human umbilical vein endothelial cells. The rLIC10365 activated endothelium in such a manner that E-selectin and intercellular adhesion molecule 1 (ICAM-1) became upregulated in a dose-dependent fashion. The LIC10365-encoded protein was identified in vivo in the renal tubules of animal during experimental infection with Leptospira interrogans. Collectively, these results implicate the LIC10365-coding protein of L. interrogans as a potential effector molecule in the promotion of a host inflammatory response. This is the first report of a leptospiral protein capable of up-regulating the expression of endothelial cell adhesion molecules ICAM-1 and E-selectin.

Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

“…Recently, a group of investigators described that the OMP of Leptospira can induce endothelial cell damage in vitro. 12 To the best of our knowledge, this study is the first to disclose endothelial glycocalyx injury in human leptospirosis. Interestingly, these alterations could be seen, even in milder forms of leptospirosis.…”

“…10 The outer membrane proteins (OMPs) of Leptospira are capable of promoting up-regulation of cell adhesion molecules (for instance, intercellular adhesion molecule-1 [ICAM-1]) expressed mainly in endothelial cells. 11,12 Although these studies were performed in vitro with umbilical vein endothelial cells, they suggested a role of endothelial activation in leptospiral pathogenesis. 11,12 Also, experimental and autopsy studies have shown endothelial necrosis and capillary thrombosis in lung tissue.…”

“…11,12 Although these studies were performed in vitro with umbilical vein endothelial cells, they suggested a role of endothelial activation in leptospiral pathogenesis. 11,12 Also, experimental and autopsy studies have shown endothelial necrosis and capillary thrombosis in lung tissue. 13,14 Another important component of the endothelium is the glycocalyx, a 1-μm carbohydrate-rich structure located at the top of the endothelium.…”

Lp95, a novel leptospiral protein that binds extracellular matrix components and activates e-selectin on endothelial cells

“…17,18,20,21 and for the pathogenic L. interrogans. 23,25 In this work, we report for the first time a L. interrogans protein, genome annotated as hypothetical, that is capable to bind laminin and fibronectin ECM components and to activate the endothelial CAM, E-selectin. The protein encoded by the LIC12690 gene is predicted to be an outer/inner membrane 29 and to be a lipoprotein.…”

“…22 We have shown that the recombinant protein rLIC10365 of L. interrogans promoted upregulation of intercellular adhesion molecule 1 (ICAM-1) and E-selectin on HUVECS. 23 More recently, we reported that three selected coding sequences (LIC10507, LIC10508 and LIC10509), located in a region of the L. interrogans serovar Copenhageni genome that has a potential involvement in pathogenesis, 24 were also capable to promote stimulation of ICAM-1 and E-selectin on monolayers of HUVECS. 25 We trust that understanding the molecular mechanism of leptospiral pathogenesis should help the identification of novel vaccine candidates.…”