Induction of experimental proteinuria in vivo following infusion of human plasma hemopexin

Cheung, Po Kam; Klok, Pieter; Baller, Jfw; Bakker, Winston W.

doi:10.1046/j.1523-1755.2000.00996.x

Cited by 89 publications

(83 citation statements)

References 23 publications

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“…Some prior studies have suggested that Hx might have intrinsic protease activity. Bakker et al identified a plasma factor 100 KF that is closely related to Hx and has protease activity that induced transient protein leakage after incubation with rat kidney ex vivo and perfusion of kidney (22,23). In a different study, protease activity was reported in recombinant Hx expressed in Pichia pastoris using an amidolytic assay, although there was no expressed control protein reported (24).…”

Section: Discussionmentioning

confidence: 99%

“…However, questions have been raised as to the safety of Hx infusion because of possible protease activity of Hx (22)(23)(24) and possible effects of Hx on neutrophil chemotaxis in a different study (25).…”

Section: Amidolytic Assaymentioning

confidence: 99%

“…The supernatants were saved at -80°C for MPO assay. The enzyme activity was determined spectrophotometrically as the MPO-catalyzed change in absorbance in the redox reaction of H 2 O 2 (450 nm with a reference filter 620 nm, 25°C), as described previously (22). MPO concentrations (mUnits/peritoneal cavity) were determined using MPO standards (Sigma).…”

Section: Myeloperoxidase (Mpo) Assaymentioning

confidence: 99%

“…Chemotaxis migration was performed in a 96-well cell migration system with 5-μL pore size, 30 μL-plate well volume be intrinsic protease activity is that these preparations have some risk of contamination by other serum proteins (22,24). Study of a recombinant version should minimize this issue.…”

Section: Human Neutrophil Chemotaxis Migration Assaymentioning

confidence: 99%

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Purified and Recombinant Hemopexin: Protease Activity and Effect on Neutrophil Chemotaxis

Tian

Liu

Feng

et al. 2016

Mol Med

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Infusion of the heme-binding protein hemopexin has been proposed as a novel approach to decrease heme-induced inflammation in settings of red blood cell breakdown, but questions have been raised as to possible side effects related to protease activity and inhibition of chemotaxis. We evaluated protease activity and effects on chemotaxis of purified plasma hemopexin obtained from multiple sources as well as a novel recombinant fusion protein Fc-hemopexin. Amidolytic assay was performed to measure the protease activity of several plasma-derived hemopexin and recombinant Fc-hemopexin. Hemopexin was added to the human monocyte culture in the presence of lipopolysaccharides (LPS), and also injected into mice intravenously (i.v.) 30 min before inducing neutrophil migration via intraperitoneal (i.p.) injection of thioglycolate. Control groups received the same amount of albumin. Protease activity varied widely between hemopexins. Recombinant Fc-hemopexin bound heme, inhibited the synergy of heme with LPS on tumor necrosis factor (TNF) production from monocytes, and had minor but detectable protease activity. There was no effect of any hemopexin preparation on chemotaxis, and purified hemopexin did not alter the migration of neutrophils into the peritoneal cavity of mice. Heme and LPS synergistically induced the release of LTB4 from human monocytes, and hemopexin blocked this release, as well as chemotaxis of neutrophils in response to activated monocyte supernatants. These results suggest that hemopexin does not directly affect chemotaxis through protease activity, but may decrease heme-driven chemotaxis and secondary inflammation by attenuating the induction of chemoattractants from monocytes. This property could be beneficial in some settings to control potentially damaging inflammation induced by heme.

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Section: Discussionmentioning

confidence: 99%

Section: Amidolytic Assaymentioning

confidence: 99%

Section: Myeloperoxidase (Mpo) Assaymentioning

confidence: 99%

Section: Human Neutrophil Chemotaxis Migration Assaymentioning

confidence: 99%

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Purified and Recombinant Hemopexin: Protease Activity and Effect on Neutrophil Chemotaxis

Tian

Liu

Feng

et al. 2016

Mol Med

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“…79 Subsequently, this group reported that 100KF/ hemopexin preparations from human serum also reduced staining of ecto-ATPases in glomeruli of kidney sections 44 as well as induced proteinuria and fusion of epithelial foot processes in glomerular capillary segments following intra-renal infusion in vivo in rats. 80 This latter observation was expanded in a recent study 24 that used cultured epithelial cells (podocytes) to provide evidence that led to the conclusion that their hemopexin preparations cause reorganization of actin fibers in podocytes through a nephrin-dependent signaling cascade. Various types of hemopexin preparations have been used in publications from the Bakker group, including recombinant hemopexin, and each merits consideration.…”

Section: Hemopexin As a Serine Proteasementioning

confidence: 97%

An alternative view of the proposed alternative activities of hemopexin

2011

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Hemopexin is a plasma protein that plays a well-established biological role in sequestering heme that is released into the plasma from hemoglobin and myoglobin as the result of intravascular or extravascular hemolysis as well as from skeletal muscle trauma or neuromuscular disease. In recent years, a variety of additional biological activities have been attributed to hemopexin, for example, hyaluronidase activity, serine protease activity, proinflammatory and anti-inflammatory activity as well as suppression of lymphocyte necrosis, inhibition of cellular adhesion, and binding of divalent metal ions. This review examines the challenges involved in the purification of hemopexin from plasma and in the recombinant expression of hemopexin and evaluates the questions that these challenges and the characteristics of hemopexin raise concerning the validity of many of the new activities proposed for this protein. As well, an homology model of the three-dimensional structure of human hemopexin is used to reveal that the protein lacks the catalytic triad that is characteristic of many serine proteases but that hemopexin possesses two highly exposed Arg-Gly-Glu sequences that may promote interaction with cell surfaces.

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Identification of new pathogenic candidates for diabetic macular edema using fluorescence‐based difference gel electrophoresis analysis

Hernández

Garcia-Ramírez

Colomé³

et al. 2013

Diabetes Metabolism Res

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Induction of experimental proteinuria in vivo following infusion of human plasma hemopexin

Abstract: It is concluded that Hx is able to induce proteinuria associated with MCD-like alterations in rat kidney in vivo.

Cited by 89 publications

References 23 publications

Purified and Recombinant Hemopexin: Protease Activity and Effect on Neutrophil Chemotaxis

Purified and Recombinant Hemopexin: Protease Activity and Effect on Neutrophil Chemotaxis

An alternative view of the proposed alternative activities of hemopexin

Identification of new pathogenic candidates for diabetic macular edema using fluorescence‐based difference gel electrophoresis analysis

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