Resistance of transgenic mice expressing human group II phospholipase A2 to Escherichia coli infection

Group II phospholipase A2 (PLA2) is a newly recognized antibacterial acute- phase protein. Recently we observed that transgenic mice expressing group I I PLA2 (PLA2(+) mice) were able to resist experimental Staphylococcus aureu s 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 establ ish the role of group II PLA2 in Escherichia coli infection, the host respo nses of PLA2(+) mice and their PLA2-deficient C57BL/6J littermates (PLA2(-) mice) were studied after intraperitoneal administration of E. coli. The le vels of group II PLA2 in sera of PLA2(+) mice increased after the administr ation of E. coli, and the concentration of group II PLA2 correlated signifi cantly with the catalytic activity of PLA2 in serum. PLA2(+) mice showed lo wer rates of mortality and less bacterial growth in peritoneal lavage fluid , blood, and spleen and liver tissues than PLA2(-) mice. Unlike the observa tions with staphylococcal infection, serum and peritoneal lavage fluid did not inhibit the growth of E. coli in vitro. The results indicate that expre ssion of the group II PLA2 transgene improves the host defense of mice agai nst E. coli infection.