Monoclonal antibodies against receptor-induced binding sites detect cell-bound plasminogen in blood.
Binding of Glu-plasminogen (the native, circulating form of the zymogen) to cells results in enhancement of its activation. Cell-associated plasmin proteolytic activity is a key component of physiologic and pathologic processes requiring extracellular matrix degradation. Recently, we developed antiplasminogen mAbs that recognize receptor-induced binding sites (RIBS) in Glu-plasminogen and, therefore, preferentially react with cell-associated Glu-plasminogen in the presence of soluble Glu-plasminogen. Here we have used FACS with a representative antiplasminogen receptor-induced binding site mAb, mAb49, to examine whether plasminogen associates with peripheral blood cells in blood. Plasminogen binding to neutrophils, monocytes, B-lymphocytes, T-lymphocytes, and platelets was clearly detected. Treatment of whole blood with lipopolysaccharide or 12-0 tetradecanoylphorbol-13-acetate up-regulated plasminogen binding to neutrophils and in vivo treatment with all-trans retinoic acid decreased plasminogen binding to acute promyelocytic leukemia blasts. Our results demonstrate that mAb49 can be used to monitor cell-bound plasminogen in blood under both normal and pathologic conditions.
ABS-Canaletes, Institut Català de la Salut, Cerdanyola del Valles, Spain.
Jordi
J
Félez
Mercè
M
Jardí
Pere
P
Fàbregas
Robert J
RJ
Parmer
Lindsey A
LA
Miles
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000918:Antibody Specificity / Q000276:immunology; D001665:Binding Sites / Q000187:drug effects / Q000276:immunology; D002273:Carcinogens / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D009504:Neutrophils / Q000166:cytology; D010958:Plasminogen / Q000276:immunology* / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D002273:Carcinogens; D008070:Lipopolysaccharides; D010958:Plasminogen; D013755:Tetradecanoylphorbol Acetate