Binding of Lys-plasminogen to monocytes/macrophages. J Clin Invest 1988 Dec;82(6):1948-55
Date
12/01/1988Pubmed ID
2974046Pubmed Central ID
PMC442776DOI
10.1172/JCI113814Scopus ID
2-s2.0-0024255824 (requires institutional sign-in at Scopus site) 48 CitationsAbstract
The ability of mononuclear phagocytes to assemble and activate components of the fibrinolytic system on their surfaces may be crucial in effecting an efficient inflammatory response. Lys-plasminogen, the plasmin modified form of this zymogen, was found to bind specifically and with high affinity to murine peritoneal macrophages and to cells of the human monocytoid line U937. This modified plasminogen has been shown to be a more efficient substrate for plasminogen activators than native Glu-plasminogen. Binding was lysine binding site dependent, rapid and reversible. In contrast, although native Glu-plasminogen bound specifically to these cells, affinity was low. Lys-plasminogen inhibited the binding of Glu-plasminogen but the opposite was not true. Molecular analysis of the bound ligands indicated that Glu-plasminogen was converted to Lys-plasminogen and Lys-plasminogen to plasmin on the cell surface but not in the supernatant. Peritoneal macrophages from patients with indwelling catheters and tissue macrophages in chronic inflammatory lesions were shown to express immunologically identified Lys-plasminogen on their surfaces. Therefore binding and surface activation of kinetically favored Lys-plasminogen may provide an important physiological mechanism for localizing proteolytic activity on the surface of inflammatory cells.
Author List
Silverstein RL, Friedlander RJ Jr, Nicholas RL, Nachman RLAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBinding Sites
Catheters, Indwelling
Cell Line
Fibrinolysin
Fibrinolysis
Inflammation
Lysine
Macrophage Activation
Macrophages
Mice
Peptide Fragments
Plasminogen
Surface Properties
