Plg‐RKT Deficient Mice Exhibit Defective Macrophage Migration and Plasminogen Binding

Abstract

Plg‐RKT is a novel transmembrane plasminogen receptor that binds plasminogen via a carboxy‐terminal lysine residue. In order to evaluate the role of Plg‐RKT in vivo we generated Plg‐RKT‐/‐ mice using homologous recombination and backcrossed the mice ten generations into the C57BL/6J background. The mice were viable and fertile. Among 2,340 littermates from heterozygous matings 611 were Plg‐RKT+/+ (26%), 1,136 were Plg‐RKT +/‐ (49%) and 593 were Plg‐RKT ‐/‐ (25%). This distribution was not significantly different (P>0.05, Chi‐square test) from the expected Mendelian 1:2:1 ratios and indicate equal viability at 3 weeks of age of Plg‐RKT +/+, Plg‐RKT +/‐, and Plg‐RKT ‐/‐ mice. Hematological parameters were determined. There was no effect of genotype on activated partial thromboplastin time, prothrombin time, plasma plasminogen and fibrinogen levels or hematocrit. Plasminogen binding to mouse macrophages was evaluated using quantitative fluorescence activated cell sorting. Plasminogen binding to Plg‐RKT ‐/‐ macrophages was only 20% of that of Plg‐RKT +/+ macrophages (Bmax = 16,386 ± 1,315 molecules/cell and 81,399 ±9,585 molecules/cell, respectively). Furthermore, macrophage migration to the peritoneum 72 hr following thioglycollate injection was 60% less in Plg‐RKT ‐/‐ mice compared to Plg‐RKT +/+ littermates. In conclusion, Plg‐RKTis required for plasminogen binding and macrophage migration in vivo, key features of the inflammatory response.