Several dehydrogenases and kinases compete for endocytosis from plasma by rat tissues

Bijsterbosch, Martin K.; Duursma, Anneke M.; Smit, Martin J.; Bos, Octaaf J.M.; Bouma, J.M.W.; Gruber, M.

doi:10.1042/bj2290409

Cited by 25 publications

(19 citation statements)

References 31 publications

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“…28 The significant reduction in KCs (CD163 ϩ cells) in liver sections from PD-0360324 -treated nonhuman primates confirmed the pharmacological effects of the drug on the tissue macrophage population. The initial observation in nonhuman primates that depletion of M-CSF leads to reductions in KCs and increases in serum enzymes is consistent with earlier reports 24,25,29 demonstrating a role for KCs in enzyme clearance. Similarly, ED2, which recognizes a membrane-bound antigen selectively expressed in the monocyte/macrophage lineage, 30,31 was significantly decreased in CLO-treated rats.…”

supporting

confidence: 78%

“…AST and ALT undergo endocytosis by nonparenchymal liver cells, including KCs and endothelial cells. 24,25 Thus, it is possible that ALT is cleared predominately by endothelial cells, whereas the depletion of KCs has a more dramatic effect on AST, leading to the observed increase in circulating concentrations. The half-lives of serum enzymes vary widely, from a few hours to several days.…”

Section: Discussionmentioning

confidence: 99%

“…Blood samples were collected before dosing and at 4,8,24,48,72,96, and 192 hours after treatment to investigate the effect of CLO-mediated KC depletion on serum levels of ALT, AST, CK, GLDH, and LDH. As expected, serum enzyme levels in rats treated with PBS were within normal limits.…”

Section: Significant Increases In Ast Ck Alt Gldh and Ldh Enzyme mentioning

confidence: 99%

“…In the CLO-treated rats, animals were observed daily for clinical signs and food consumption. Clinical chemistry parameters [alanine aminotransferase (ALT), AST, CK, glutamate dehydrogenase (GLDH), and LDH] were evaluated in samples collected before dosing and at 4,8,24,48,72,96, and 192 hours after liposome administration. Animals were euthanized at 24, 72, and 192 hours after liposome administration.…”

Section: Experimental Design Of the Dichloromethylenebisphosphonate Kmentioning

confidence: 99%

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Increased Serum Enzyme Levels Associated with Kupffer Cell Reduction with No Signs of Hepatic or Skeletal Muscle Injury

Radi

Koza-Taylor

Bell

et al. 2011

The American Journal of Pathology

121

101

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Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that is responsible for the survival and proliferation of monocytes and the differentiation of monocytes into macrophages, including Kupffer cells (KCs) in the liver. KCs play an important role in the clearance of several serum enzymes, including aspartate aminotransferase and creatine kinase, that are typically elevated as a result of liver or skeletal muscle injury. We used three distinct animal models to investigate the hypothesis that increases in the levels of serum enzymes can be the result of decreases in KCs in the apparent absence of hepatic or skeletal muscle injury. Specifically, neutralizing M-CSF activity via a novel human monoclonal antibody reduced the CD14 ؉ CD16 ؉ monocyte population, depleted KCs, and increased aspartate aminotransferase and creatine kinase serum enzyme levels in cynomolgus macaques. In addition, the treatment of rats with clodronate liposomes depleted KCs and led to increased serum enzyme levels, again without evidence of tissue injury. Finally, in the osteopetrotic (Csf1 op /Csf1 op ) mice lacking functional M-CSF and having reduced levels of KCs, the levels of serum enzymes are higher than in wild-type littermates. Together, these findings support a mechanism for increases in serum enzyme levels through M-CSF regulation of tissue macrophage homeostasis without concomitant histopathological changes in either the hepatic or skeletal system.

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supporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Significant Increases In Ast Ck Alt Gldh and Ldh Enzyme mentioning

confidence: 99%

Section: Experimental Design Of the Dichloromethylenebisphosphonate Kmentioning

confidence: 99%

See 2 more Smart Citations

Increased Serum Enzyme Levels Associated with Kupffer Cell Reduction with No Signs of Hepatic or Skeletal Muscle Injury

Radi

Koza-Taylor

Bell

et al. 2011

The American Journal of Pathology

121

101

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“…Por otra parte, están los marcadores bioquímicos indicadores del daño muscular: el tejido muscular puede ser dañado como consecuencia de factores mecánicos y metabólicos (Brancaccio, Lippi, Nicola Maffulli, 2010;Bijsterbosch, Duursma A, Smit, Bos, Bouma, Gruber, 1985). De hecho, la rabdomiolisis por esfuerzo puede resultar de un daño directo e indirecto de la membrana muscular, produciendo un transvase de ciertos componentes de la membrana hacia el líquido extracelular (Brancaccio y col. 2010;Bijsterbosch y col., 1985).…”

Section: Introductionunclassified

Monitorización de biomarcadores sanguíneos en jugadores profesionales de fútbol durante la fase preparatoria y competitiva. [Monitoring biochemical markers in professional soccer players during the season and preseason preparation phase].

Vilamitjana¹,

Vaccari²,

Toedtli³

et al. 2017

Rev. int. cienc. deporte

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Drug targeting to the liver with lactosylated albumins: Does the glycoprotein target the drug or is the drug targeting the glycoprotein?

et al. 1986

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The isolated perfused rat liver preparation was employed to study hepatic disposition of the model drug-carrier conjugate fluorescein-lactosylated albumin (F-LnHSA) with special reference to the influence of the organic anion fluorescein on liver cell specificity of the endocytosed neoglycoprotein. Hepatic clearance of fluoresceinated neoglycoproteins was significantly faster than clearance of radioiodinated neoglycoproteins. Perfusate clearance of F-L7HSA and F-L25HSA could not completely be inhibited by a dose of 10 mg asialoorosomucoid that saturates the hepatocyte receptor-mediated endocytic process. From these data, we inferred an additional hepatic uptake mechanism, competing with the Ashwell-receptor-mediated internalization of galactose-terminated glycoproteins. Clearance experiments with fluoresceinated 125I-human serum albumin in the presence of the polyanionic probe dextran sulfate revealed a nearly complete (approximately 90%) inhibition of hepatic uptake, while also a pronounced effect was obtained with colloidal carbon. These data point to nonparenchymal cell uptake of fluoresceinated protein via interaction with scavenger receptors. In wash-out studies, it was shown that about 25% of ligand sequestrated by sinusoidal liver cells escaped degradation and recycled to the perfusion medium. Our results show that care should be taken in the use of neoglycoproteins as drug carriers to hepatocytes, since a load of only 2 to 3 moles fluorescein per mole neoglycoprotein considerably affects intrahepatic distribution. The relative contribution of nonparenchymal cell uptake by coupling of acidic drugs to the neoglycoproteins is very probably inversely related to the number of exposing galactose groups per molecule neoglycoprotein. This phenomenon of "inversed targeting" could therapeutically both be useful or detrimental, dependent on the spectrum of cell types that should be reached by the drug.

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Several dehydrogenases and kinases compete for endocytosis from plasma by rat tissues

Cited by 25 publications

References 31 publications

Increased Serum Enzyme Levels Associated with Kupffer Cell Reduction with No Signs of Hepatic or Skeletal Muscle Injury

Increased Serum Enzyme Levels Associated with Kupffer Cell Reduction with No Signs of Hepatic or Skeletal Muscle Injury

Monitorización de biomarcadores sanguíneos en jugadores profesionales de fútbol durante la fase preparatoria y competitiva. [Monitoring biochemical markers in professional soccer players during the season and preseason preparation phase].

Drug targeting to the liver with lactosylated albumins: Does the glycoprotein target the drug or is the drug targeting the glycoprotein?

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