Modulation of plasminogen activator secretion by activated macrophages: influence of serum factors and correlation with tumoricidal potential. 1979

H A Chapman, and Z Vavrin, and J B Hibbs

A high molecular weight fraction of human serum (Fr-1) was found to both inhibit macrophage tumoricidal activity and enhance plasminogen activator activity in supernates over activated macrophages in vitro. Conversely, a 40- to 90-kilodalton serine esterase (Fr-3) also found in normal human serum and endotoxin enhanced tumoricidal potential and suppressed the supernatant plasminogen activator activity. Inactivation of either Fr-1 or Fr-3 by 2-mercaptoethanol or diisopropyl fluorophosphate, respectively, abolished both biologic effects. Examination of cell-associated and culture medium plasminogen activator activity before and after acidification to inactivate proteinase inhibitors indicated that suppression of plasminogen activator activity by Fr-3 or endotoxin most likely represents modulation of macrophage plasminogen activator secretion. The findings demonstrate that activated macrophages are capable of highly coordinated biologic responses to alterations in their microenvironment and suggest that it is in fact the high potential for such responsiveness that reliably characterizes the activated macrophage. The results also suggest that an endogenous regulatory system dependent on the interaction of serine esterases may operate to regulate the functional capabilities of activated macrophages.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D010960 Plasminogen Activators A heterogeneous group of proteolytic enzymes that convert PLASMINOGEN to FIBRINOLYSIN. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. Extrinsic Plasminogen Activators,Plasminogen Activator,Uterine-Tissue Plasminogen Activator,Uterine Tissue Plasminogen Activator
D001769 Blood The body fluid that circulates in the vascular system (BLOOD VESSELS). Whole blood includes PLASMA and BLOOD CELLS.
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004731 Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Endotoxin
D004950 Esterases Any member of the class of enzymes that catalyze the cleavage of an ester bond and result in the addition of water to the resulting molecules. Esterase
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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