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Published on: April 9, 2018
Resistance of transgenic mice expressing human group II phospholipase A2 to Escherichia coli infection
V J Laine1, D S Grass, T J Nevalainen
1Department of Pathology, University of Turku, 20520 Turku, Finland. vellai@utu.fi
Abstract:
Group II phospholipase A2 (PLA2) is a newly recognized antibacterial acute-phase protein. Recently we observed that transgenic mice expressing group II PLA2 (PLA2(+) mice) were able to resist experimental Staphylococcus aureus infection by killing the bacteria, as indicated by improved survival and by the small numbers of live bacteria in their tissues (V. J. O. Laine, D. S. Grass, and T. J. Nevalainen, J. Immunol. 162:7402-7408, 1999). To establish the role of group II PLA2 in Escherichia coli infection, the host responses of PLA2(+) mice and their PLA2-deficient C57BL/6J littermates (PLA2(-) mice) were studied after intraperitoneal administration of E. coli. The levels of group II PLA2 in sera of PLA2(+) mice increased after the administration of E. coli, and the concentration of group II PLA2 correlated significantly with the catalytic activity of PLA2 in serum. PLA2(+) mice showed lower rates of mortality and less bacterial growth in peritoneal lavage fluid, blood, and spleen and liver tissues than PLA2(-) mice. Unlike the observations with staphylococcal infection, serum and peritoneal lavage fluid did not inhibit the growth of E. coli in vitro. The results indicate that expression of the group II PLA2 transgene improves the host defense of mice against E. coli infection.
Insights
Group II phospholipase A2 (PLA2) enhances host defense against bacterial infections. Transgenic mice expressing group II PLA2 showed improved survival and reduced bacterial growth during Escherichia coli infection.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Group II phospholipase A2 (PLA2) is an acute-phase protein with recognized antibacterial properties.
- Previous studies demonstrated that transgenic mice expressing group II PLA2 resisted Staphylococcus aureus infection.
Purpose of the Study:
- To investigate the role of group II PLA2 in host defense against Escherichia coli infection.
- To compare the responses of group II PLA2-expressing mice and PLA2-deficient mice to E. coli challenge.
Main Methods:
- Transgenic mice overexpressing group II PLA2 (PLA2(+) mice) and their PLA2-deficient littermates (PLA2(-) mice) were used.
- Mice were infected intraperitoneally with Escherichia coli.
- Survival rates, bacterial loads in tissues and fluids, and in vitro bacterial growth inhibition were assessed.
Main Results:
- Group II PLA2 levels and activity in serum increased in PLA2(+) mice following E. coli administration.
- PLA2(+) mice exhibited significantly lower mortality rates compared to PLA2(-) mice.
- Reduced bacterial growth was observed in peritoneal lavage fluid, blood, spleen, and liver of PLA2(+) mice.
- In vitro studies showed no direct inhibition of E. coli growth by serum or peritoneal lavage fluid from PLA2(+) mice.
Conclusions:
- Expression of the group II PLA2 transgene confers enhanced resistance to Escherichia coli infection in mice.
- Group II PLA2 plays a crucial role in the host immune response against E. coli, independent of direct in vitro bactericidal activity.
- These findings highlight the therapeutic potential of group II PLA2 in combating bacterial infections.
