Induction of glomerular alkaline phosphatase after challenge with lipopolysaccharide

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Abstract
Summary.  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, TNFα or IL‐6, and mRNA for AP was studied in TNFα‐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, TNFα or IL‐6, whereas increased mRNA for AP was observed in mesangial cells after TNFα 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.