Lp25 membrane protein from pathogenic Leptospira spp. is associated with rhabdomyolysis and oliguric acute kidney injury in a guinea pig model of leptospirosis

Abreu, Patrícia Antônia Estima; Seguro, Antônio Carlos; Canale, Daniele; Silva, Ana G.; Matos, Larissa do Rêgo Barros; Gotti, Tatiane B.; Monaris, Denize; Jesus, Denise A. de; Vasconcellos, Sílvio Arruda; Brito, Thales de; Magaldi, Antonio J.

doi:10.1371/journal.pntd.0005615

Cited by 20 publications

(33 citation statements)

References 46 publications

(59 reference statements)

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“…Recently, it was also shown, in normal guinea pigs that Lp25, a surface protein of pathogenic leptospires, was partially responsible for hyperkalemic pre-renal acute kidney manifestations induced by rhabdomyolysis 39 . Pathology demonstrated in this experiment, that there is no wide range of muscle fiber sizes nor small or large groups of atrophic or hypertrophic fibers.…”

Section: Muscular Lesionsmentioning

confidence: 99%

Pathology and pathogenesis of human leptospirosis: a commented review

Brito

Silva

Abreu

2018

Rev. Inst. Med. trop. S. Paulo

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Leptospirosis is an acute bacterial septicemic febrile disease caused by pathogenic leptospires, which affect humans and animals in all parts of the world. Transmission can occur by direct contact with infected animals or, more commonly, through indirect contact with water or soil contaminated with urine from infected animals. Leptospires enter the body by penetrating mucous membranes or skin abrasions and disseminate through the hematogenic route. In humans, leptospirosis may cause a wide spectrum of symptoms. Most cases have a biphasic clinical presentation, which begins with the septicemic phase followed by immune manifestations. The severe forms of the disease may be life threatening with multisystem damage including renal failure, hepatic dysfunction, vascular damage, pulmonary hemorrhage and muscle lesions. In this review, we present and discuss the pathogenesis of the human disease and the mechanisms of cell membrane injuries, which occur mainly due to the presence of leptospires and/or their antigen/s in the host tissues.

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Section: Muscular Lesionsmentioning

confidence: 99%

Pathology and pathogenesis of human leptospirosis: a commented review

Brito

Silva

Abreu

2018

Rev. Inst. Med. trop. S. Paulo

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“…Even so, the bacterial load would have been much lower than that observed in the liver. The pathogenesis of acute kidney injury in leptospirosis is the direct nephrotoxic action of the leptospira infection and toxins release, but hemodynamic alteration, jaundice, and rhabdomyolysis (a disruption of skeletal muscle integrity) are also associated (Daher Ede et al, 2010 ; Abreu et al, 2017 ). Taking together the biochemical assay results regarding the elevation of AST only in C5 −/− mice on the third day post infection and uric acid in both mice on the sixth day post infection, we can suggest that the infection may be inducing rhabdomyolysis in a manner independent of C5.…”

Section: Discussionmentioning

confidence: 99%

Role of Murine Complement Component C5 in Acute in Vivo Infection by Pathogenic Leptospira interrogans

Castro

Bavia

Fraga

et al. 2018

Front. Cell. Infect. Microbiol.

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Leptospirosis is considered one of the most important zoonosis worldwide. The activation of the Complement System is important to control dissemination of several pathogens in the host. Only a few studies have employed murine models to investigate leptospiral infection and our aim in this work was to investigate the role of murine C5 during in vivo infection, comparing wild type C57BL/6 (B6 C5+/+) and congenic C57BL/6 (B6 C5−/−, C5 deficient) mice during the first days of infection. All animals from both groups survived for at least 8 days post-infection with pathogenic Leptospira interrogans serovar Kennewicki strain Fromm (LPF). At the third day of infection, we observed greater numbers of LPF in the liver of B6 C5−/− mice when compared to B6 C5+/+ mice. Later, on the sixth day of infection, the LPF population fell to undetectable levels in the livers of both groups of mice. On the third day, the inflammatory score was higher in the liver of B6 C5+/+ mice than in B6 C5−/− mice, and returned to normal on the sixth day of infection in both groups. No significant histopathological differences were observed in the lung, kidney and spleen from both infected B6 C5+/+ than B6 C5−/− mice. Likewise, the total number of circulating leukocytes was not affected by the absence of C5. The liver levels of IL-10 on the sixth day of infection was lower in the absence of C5 when compared to wild type mice. No significant differences were observed in the levels of several inflammatory cytokines when B6 C5+/+ and B6 C5−/− were compared. In conclusion, C5 may contribute to the direct killing of LPF in the first days of infection in C57BL/6 mice. On the other hand, other effector immune mechanisms probably compensate Complement impairment since the mice survival was not affected by the absence of C5 and its activated fragments, at least in the early stage of this infection.

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“…With the exception of ABO-incompatible blood transfusions, haemolysis is now considered a contributing, rather than sole, trigger in the pathogenesis of haemoglobinuria-related AKI [9]. In fact, some conditions such as poisoning, envenomation and leptospirosis, may present with both haemolysis and rhabdomyolysis [88,[95][96][97][98]. Furthermore, in malaria-associated AKI, other mechanisms play a greater pathogenic role than haemolysis, including mechanic obstruction by parasitized RBCs, the pro-inflammatory cytokine storm and immunecomplex deposition [9,99].…”

Section: Haemoglobin-mediated Pigment Nephropathymentioning

confidence: 99%

Pigment Nephropathy: Novel Insights into Inflammasome-Mediated Pathogenesis

Giuliani

Kassianos

Healy

et al. 2019

Preprint

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Pigment nephropathy is an acute decline in renal function following the deposition of endogenous haem-containing proteins in the kidneys. Haem pigments such as myoglobin and haemoglobin are filtered by glomeruli and absorbed by the proximal tubules. They cause renal vasoconstriction, tubular obstruction, increased oxidative stress and inflammation. Haem is associated with inflammation in sterile and infectious conditions, contributing to the pathogenesis of many disorders such as rhabdomyolysis and haemolytic diseases. In fact, haem appears to be a signaling molecule that is able to activate the inflammasome pathway. Recent studies highlight a pathogenic function for haem in triggering inflammatory responses through the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Among the inflammasome multiprotein complexes, the NLRP3 inflammasome has been the most widely characterized as a trigger of inflammatory caspases and the maturation of interleukin-18 and -1β. In the present review, we discuss the latest evidence on the importance of inflammasome-mediated inflammation in pigment nephropathy. Finally, we highlight the potential role of inflammasome inhibitors in the prophylaxis and treatment of pigment nephropathy.

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Lp25 membrane protein from pathogenic Leptospira spp. is associated with rhabdomyolysis and oliguric acute kidney injury in a guinea pig model of leptospirosis

Cited by 20 publications

References 46 publications

Pathology and pathogenesis of human leptospirosis: a commented review

Pathology and pathogenesis of human leptospirosis: a commented review

Role of Murine Complement Component C5 in Acute in Vivo Infection by Pathogenic Leptospira interrogans

Pigment Nephropathy: Novel Insights into Inflammasome-Mediated Pathogenesis

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