Resistance of Transgenic Mice Expressing Human Group II Phospholipase A2 toEscherichia coliInfection

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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 experimentalStaphylococcus aureusinfection 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 inEscherichia coliinfection, the host responses of PLA2+mice and their PLA2-deficient C57BL/6J littermates (PLA2−mice) were studied after intraperitoneal administration ofE. coli. The levels of group II PLA2 in sera of PLA2+mice increased after the administration ofE. 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 ofE. coliin vitro. The results indicate that expression of the group IIPLA2transgene improves the host defense of mice againstE. coliinfection.