Induction of glomerular alkaline phosphatase after challenge with lipopolysaccharide.
Alkaline phosphatase (AP) can be considered as a host defence molecule since this enzyme is able to detoxify bacterial endotoxin at physiological pH. The question emerged whether this anti-endotoxin principle is inducible in the glomerulus and if so, which glomerular cells might be involved in the expression of ectoAP after stimulation with pro-inflammatory agents. Therefore kidneys of rats treated with either lipopolysaccharide (LPS), E. coli bacteria or non-toxic monophosphoryl lipid A (MPLA) were examined for AP activity 6 or 24 h after challenge. In addition cultures of endothelial cells or mesangial cells were evaluated for AP activity after stimulation with either LPS, TNFalpha or IL-6, and mRNA for AP was studied in TNFalpha-stimulated and control mesangial cells. The results show significant up-regulation of glomerular AP in LPS- or E. coli-injected rats compared to rats injected with MPLA. Endothelial and mesangial cells in vitro showed significant up-regulation of AP activity following stimulation with LPS, TNFalpha or IL-6, whereas increased mRNA for AP was observed in mesangial cells after TNFalpha stimulation compared to non-stimulated control cells. Since it appeared that hydrolysis occurred when endotoxin was used as a substrate in the histochemical staining, we concluded that inducible glomerular ectoAP may reflect a local endotoxin detoxifying principle of the kidney.
Kapojos
Jola J
JJ
Department of Pathology and Laboratory Medicine, University of Groningen, The Netherlands.
Poelstra
Klaas
K
Borghuis
Theo
T
Van Den Berg
Anke
A
Baelde
Hans J
HJ
Klok
Pieter A
PA
Bakker
Winston W
WW
D000469:Alkaline Phosphatase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation; D004926:Escherichia coli; D005260:Female; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology; D015850:Interleukin-6 / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000201:enzymology* / Q000382:microbiology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015850:Interleukin-6; D008050:Lipid A; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000469:Alkaline Phosphatase; C048436:monophosphoryl lipid A