Lysosomal hydrolases of human vascular cells: response to agonists of endothelial function.
Endothelial injury has been proposed as a feature of a wide variety of vascular diseases, and release of endothelial lysosomal hydrolases could contribute to the pathological changes seen. We have determined the relative activities of 14 glycosidases, two esterases and four peptide hydrolases in human umbilical vein endothelial cells and investigated whether known agonists of endothelial function, or materials known to modulate hydrolase secretion in other phagocytic cells, influenced the activity or secretion of these enzymes by human umbilical vein endothelial cells. Hexosaminidase, beta-galactosidase, beta-glucuronidase and alpha-iduronidase accounted for most of the measured glycosidase activity. Acid phosphatase activity greatly exceeded arylsulphatase activity, and most of the measured peptidase activity was due to acid peptidases. Optimum pH and apparent Km values were determined for the most abundant hydrolases. Exposure of human umbilical vein endothelial cells to bradykinin, thrombin or interleukin-1 resulted in negligible release of either hexosaminidase or lactate dehydrogenase (LDH), in contrast to phorbol myristate acetate, which caused a parallel, dose-dependent release of both enzymes. Treatment of these cells with calcium ionophore A23187, trypsin or platelet-activating factor, caused less than 10% release of either hexosaminidase or LDH. Agents known to modulate lysosomal enzyme secretion by other phagocytic cells failed to induce selective secretion of lysosomal enzymes by human umbilical vein endothelial cells.
Morgan
D M
DM
Section of Vascular Biology, Medical Research Council Clinical Research Centre, Harrow, Middlesex, U.K.
Pearson
J D
JD
Gordon
J L
JL
D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D004950:Esterases / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D007375:Interleukin-1 / Q000502:physiology*; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000502:physiology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D006867:Hydrolases; D004950:Esterases; D006026:Glycoside Hydrolases; D010447:Peptide Hydrolases; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin