Interactions of Shiga-like toxin with human peripheral blood monocytes

The cytotoxic effect of Shiga-like toxin (Stx; produced by certain Escherichia coli strains) plays a central role in typical hemolytic uremic syndrome (HUS). It damages the renal endothelium by inhibiting the cellular protein synthesis. Also, the monocyte has a specific receptor for Stx but is not sensitive for the cytotoxic effect. In this work, monocytes were studied as a potential transporter for Stx to the renal endothelium. Coincubation of isolated human monocytes loaded with Stx and target cells (vero cells and human umbilical vascular endothelial cells) were performed. Transfer was determined by measuring the protein synthesis of target cells and by flow cytometry. Furthermore, the effect of a temperature shift on loaded monocytes was investigated. Stx-loaded monocytes reduced the protein synthesis of target cells. After adding an antibody against Stx, incomplete recovery occurred. Also, adding only the supernatant of coincubation was followed by protein synthesis inhibition. Stx detached from its receptor on the monocyte after a change in temperature, and no release was detected without this temperature shift. Although the monocyte plays an important role in the pathogenesis of HUS, it has no role in the transfer of Stx

Molecular genetic analysis of podocyte genes in focal segmental glomerulosclerosis—a review

This review deals with podocyte proteins that play a significant role in the structure and function of the glomerular filter. Genetic linkage studies has identified several genes involved in the development of nephrotic syndrome and contributed to the understanding of the pathophysiology of glomerular proteinuria and/or focal segmental glomerulosclerosis. Here, we describe already well-characterized genetic diseases due to mutations in nephrin, podocin, CD2AP, alpha-actinin-4, WT1, and laminin β2 chain, as well as more recently identified genetic abnormalities in TRPC6, phospholipase C epsilon, and the proteins encoded by the mitochondrial genome. In addition, the role of the proteins which have shown to be important for the structure and functions by gene knockout studies in mice, are also discussed. Furthermore, some rare syndromes with glomerular involvement, in which molecular defects have been recently identified, are briefly described. In summary, this review updates the current knowledge of genetic causes of congenital and childhood nephrotic syndrome and provides new insights into mechanisms of glomerular dysfunction

Age differences in renal response to atrial natriuretic peptide in rabbits

Plasma levels of atrial natriuretic peptide (ANP) and the effect of exogenous ANP on renal function have been studied in newborn and adult rabbits. In order to investigate an age difference in responsiveness to ANP, we studied the renal effects of alpha-human ANP (1-28) administered at the same dose per kg body weight in adult and neonatal rabbits. Plasma basal ANP levels were similar in 18 newborn (4- to 11-day-old) compared to 7 adult rabbits (150 +/- 16 and 151 +/- 28 pg/ml, resp.). Eleven newborn and 11 adult rabbits were anesthetized and mechanically ventilated. After a control period, each animal received an hANP loading dose (3 micrograms/kg i.v.), followed by an infusion of 0.3 micrograms/kg/min. Blood gases remained stable throughout the experiment in both groups. Mean blood pressure decreased in newborn (28.5 +/- 0.8 to 26.2 +/- 1.0 mmHg) and adult (92 +/- 3 to 84 +/- 3 mmHg) animals. Percent hANP-induced changes in renal functions in newborn and adult rabbits were, respectively: urine flow rate: -21 +/- 4% and +57 +/- 8%; urinary sodium excretion: +4 +/- 7% and +81 +/- 11%; glomerular filtration rate (GFR): -19 +/- 4% and -4 +/- 6%; renal blood flow (RBF): -22 +/- 4% and -11 +/- 5%. As expected, diuresis and natriuresis increased in adult rabbits. Failure of hANP to increase natriuresis and diuresis in newborn rabbits could be related to the marked decrease in GFR, receptor immaturity and/or interactions with other hormonal systems