Detection of bile salt-dependent lipase, a 110 kDa pancreatic protein, in urines of healthy subjects

Abstract

Bile salt-dependent lipase (BSDL), a 110 kDa glycoprotein secreted by the pancreatic acinar cells, participates in the duodenal hydrolysis of dietary lipid esters. Recent in vitro and in vivo studies demonstrated that the BSDL reaches the blood via a transcytosis motion through enterocytes, suggesting that this enzyme may play a role in vascular biology. Once in the blood, BSDL should be eliminated. We address the hypothesis that BSDL may be filtered by the glomerulus and eliminated in urines. Immunological methods and proteomic were used to detect and to characterize BSDL in urine. The immunoreactive form of BSDL was detected in urines of 36 male subjects devoid of renal failure. Proteomic demonstrated that the immunoreactive protein is BSDL. Experiments using a monoclonal antibody to the oncofetal glycoform of pancreatic BSDL suggested that the protein is not expressed by renal cells but originates from the pancreas via circulation. We demonstrate that under normal physiological conditions, BSDL, a high-molecular weight blood glycoprotein, can be filtered by the renal glomerulus to be eliminated in urines.

Distribution of α-Galactosidase A in Normal Human Kidney and Renal Accumulation and Distribution of Recombinant α-Galactosidase A in Fabry Mice

“…The glomerular filtration barrier for proteins has generally been considered to be in the range of albumin, which has a glomerular filtration fraction of Ͻ0.01 (21). However, we have shown that transferrin, 80 kD, is filtered to some extent normally both in human kidney and in rats and mice (22), and recently a 110-kD pancreatic lipase was found in the urine of healthy humans (23). These results support the observations of this study of a limited but significant glomerular filtration of recombinant ␣-Gal A in ␣-Gal A-deficient mice and patients, and this filtration is probably even more pronounced in patients with Fabry-Anderson disease and proteinuria.…”

Endocytosis provides a major alternative pathway for lysosomal biogenesis in kidney proximal tubular cells

“…We propose to reassess the significance and usefulness of this assay. Although glomerular filtration of a 130-kDa-large protein is obviously questionable, transferrin (80 kDa) and even bile salt-dependent lipase (110 kDa) are filtered under normal conditions (22,23), and increased glomerular leakage will increase filtered levels. Because cathepsin B has a much lower molecular weight, and consequently a much higher filtration coefficient than N-acetyl-␤-glucosaminidase, we suggest that cathepsin B could be an alternative marker for tubular dysfunction in glomerular disease.…”

Endocytosis of Secreted Carboxyl Ester Lipase in a Syndrome of Diabetes and Pancreatic Exocrine Dysfunction

“…Pancreatic CEL is transported from the duodenum via enterocytes to the blood (7), where it associates with low density lipoprotein (8). The protein is cleared from the circulation by renal glomerulus filtration and can be detected in the urine of healthy individuals (9).…”