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Lymphokine-induced secretion of plasminogen activator by murine macrophages
Abstract:
Thioglycollate-stimulated macrophages are known to release a plasminogen activator (PA) into the medium. In this study it was investigated whether macrophages could be activated to release PA after exposure to lymphokines. Macrophage monolayers obtained by 24 h culture of proteose peptone-elicited murine exudate cells were incubated with lymphocyte culture supernatants. After 48 h the supernatants were replaced by serum-free medium and the macrophages were incubated for another 24-48 h. These supernatants were assayed for PA as measured by the lysis of 125I-labeled fibrin. The following results were obtained: (a) Supernatants of antigen or mitogen-stimulated spleen cells induced PA secretion by macrophages whereas control supernatants were ineffective. The same was found with supernatants of mitogen-stimulated lymph node cells. (b) PA secretion by macrophages seems to be induced by a rather narrow concentration range of lymphokines. (c) Lymphokine-induced PA secretion by macrophages is enhanced after phagocytosis of latex beads. The results show that PA secretion by activated macrophages can be considered as a parameter of immunoactivation.
Insights
Lymphokines activate macrophages to release plasminogen activator (PA). This immune response, measurable via fibrinolysis, indicates macrophage immunoactivation and is enhanced by phagocytosis.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Macrophages stimulated by thioglycollate are known to secrete plasminogen activator (PA).
- The role of lymphokines in modulating macrophage PA secretion remains to be fully elucidated.
Purpose of the Study:
- To investigate whether lymphokines can activate macrophages to release plasminogen activator (PA).
- To assess PA secretion as a marker of macrophage immunoactivation.
Main Methods:
- Murine macrophage monolayers were incubated with supernatants from stimulated lymphocyte cultures.
- Plasminogen activator (PA) activity in culture supernatants was quantified using 125I-labeled fibrin lysis assay.
- Macrophage phagocytosis of latex beads was employed to assess its effect on lymphokine-induced PA secretion.
Main Results:
- Supernatants from antigen or mitogen-stimulated spleen and lymph node cells induced significant PA secretion by macrophages.
- Control supernatants did not induce PA secretion, indicating specificity of lymphokine action.
- Lymphokine-induced PA secretion was observed within a narrow concentration range and was enhanced by concurrent phagocytosis of latex beads.
Conclusions:
- Lymphokines derived from stimulated lymphocytes can activate macrophages to secrete plasminogen activator (PA).
- Macrophage PA secretion serves as a quantifiable parameter of immunoactivation.
- Phagocytic activity can modulate lymphokine-induced PA release, suggesting complex immune regulation.