Inflammatory mediators in human renal dysplasia.
BACKGROUND
Cytokines regulate many processes in the immune system and have recently been implicated in normal organogenesis. We previously demonstrated that the archetypal inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) is expressed in the murine metanephros, and exogenous TNF-alpha inhibits nephrogenesis and increases macrophage numbers in vitro (Cale et al., Int J Dev Biol 1998; 42: 663-674). The phenotype seen, with an arrest of ureteric bud branching and failure of mesenchymal to epithelial conversion, is similar to human renal dysplasia. Methods and results. In normal human fetal kidneys we demonstrated the presence of macrophages and T cells and also documented TNF receptor expression on ureteric bud derivatives. In contrast to normal tissues, TNF-alpha protein was detected in dysplastic kidneys. This factor was also detected in the urine of fetuses with obstructive uropathy and TNF receptors were expressed in dysplastic tubules. Furthermore, we noted a fetal distribution of macrophages and T cells in dysplastic tissues and persistent expression of the adhesion molecules neural cell adhesion molecule and intercellular adhesion molecule.


CONCLUSIONS
We suggest that abnormal expression of cytokines early in renal development dysregulates normal patterns of adhesion molecule expression and inflammatory cells, and may contribute to the pathogenesis of renal dysplasia.
Cale
C M
CM
Nephrourology Unit and Immunobiology Unit, Institute of Child Health, UCLMS, London, UK.
Klein
N J
NJ
Winyard
P J
PJ
Woolf
A S
AS
D015703:Antigens, CD / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D016922:Cellular Senescence; D005333:Fetus / Q000378:metabolism; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D017252:CD3 Complex; D018836:Inflammation Mediators; D019006:Neural Cell Adhesion Molecules; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1