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Plasminogen activator production by bovine milk macrophages and blood monocytes
I Politis1, X Zhao, B W McBride
1Department of Animal Science, McGill University, Ste Anne de Bellevue, Quebec.
Abstract:
The type of plasminogen activator (PA) produced by bovine milk macrophages has been determined. Macrophages produce a PA protein with molecular weight of 28,000 and isoelectric point of 8.5, and with enzymatic activity independent of fibrin. These characteristics are identical to those reported for bovine urokinase-PA. Although blood monocytes and milk macrophages produce PA after stimulation with lipopolysaccharide, mammary macrophages are clearly limited in their ability to release PA. At maximal stimulation, 78% of the PA produced by milk macrophages remained cell-associated. In marked contrast, blood monocytes released 76% of the PA produced into the culture medium. Macrophages isolated from mastitic quarters produced higher (2.5 times) amounts of PA, compared with those produced by macrophages isolated from healthy quarters. However, in both cases, macrophages were unable to secrete the protein already produced. The limited PA secretion by milk macrophages might be a residual function of a differentiated macrophage population.
Insights
Bovine milk macrophages produce urokinase-type plasminogen activator (uPA) but struggle to secrete it. Even during mastitis, these immune cells retain most of the uPA within the cell.
Area of Science:
- Veterinary Immunology
- Cell Biology
- Biochemistry
Background:
- Plasminogen activators (PAs) are crucial for fibrinolysis and tissue remodeling.
- Macrophages play a key role in immune responses and tissue homeostasis.
- Bovine milk macrophages are a unique population with specialized functions.
Purpose of the Study:
- To characterize the plasminogen activator (PA) produced by bovine milk macrophages.
- To investigate the secretion capacity of these macrophages compared to blood monocytes.
- To determine if PA production or secretion is altered during mastitis.
Main Methods:
- Isolation and culture of bovine milk macrophages and blood monocytes.
- Stimulation with lipopolysaccharide (LPS).
- Measurement of PA activity and quantification of cell-associated vs. secreted PA.
Main Results:
- Bovine milk macrophages produce a PA identical to bovine urokinase-PA (Mr 28,000, pI 8.5).
- Unlike blood monocytes, milk macrophages retain a significant amount (78%) of produced PA intracellularly.
- Macrophages from mastitic quarters produced 2.5 times more PA but still exhibited limited secretion.
Conclusions:
- Bovine milk macrophages produce a fibrin-independent urokinase-type PA.
- Impaired PA secretion by milk macrophages may reflect a differentiated state.
- Limited PA release could impact local tissue remodeling and immune regulation in the mammary gland.
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