Binding of Lys-plasminogen to monocytes/macrophages.
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.
Silverstein
R L
RL
Department of Medicine, Cornell University Medical College, New York, New York 10021.
Friedlander
R J
RJ
Nicholas
R L
RL
Nachman
R L
RL
D000818:Animals; D001665:Binding Sites; D002408:Catheters, Indwelling; D002460:Cell Line; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D007249:Inflammation / Q000276:immunology; D008239:Lysine / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D013499:Surface Properties
D010446:Peptide Fragments; C018998:lysyl-plasminogen; D010958:Plasminogen; D005341:Fibrinolysin; D008239:Lysine