Deficiency of plasminogen receptor, Plg-R(KT) , causes defects in plasminogen binding and inflammatory macrophage recruitment in vivo.

Essentials Plg-R(KT) is a novel integral membrane plasminogen receptor. The functions of Plg-R(KT) in vivo are not known. Plg-R(KT) is a key player in macrophage recruitment in the inflammatory response in vivo. Plg-R(KT) deficiency is not compatible with survival of the species. SUMMARY: Background Plg-R(KT) is a novel integral membrane plasminogen receptor that binds plasminogen via a C-terminal lysine exposed on the cell surface and promotes plasminogen activation on the cell surface by both tissue plasminogen activator and urokinase plasminogen activator. Objectives To evaluate the role of Plg-R(KT) in vivo we generated Plg-R(KT)(-/-) mice using a homologous recombination technique. Methods We characterized the effect of Plg-R(KT) deletion on reproduction, viability, health and spontaneous thrombosis and inflammation. Results Plg-R(KT)(-/-) mice were viable and fertile. Survival of Plg-R(KT)(-/-) mice and Plg-R(KT)(+/+) littermates was not significantly different. However, quite strikingly, all pups of Plg-R(KT)(-/-) females died within 2 days of birth, consistent with a lactation defect in Plg-R(KT)(-/-) mothers. Additionally, there was a significant effect of Plg-R(KT) deficiency on the growth rates of female, but not male, mice. In experimental peritonitis studies, Plg-R(KT)(-/-) mice exhibited a marked defect in macrophage recruitment. As a contributing mechanism, the capacity of Plg-R(KT)(-/-) macrophages for plasminogen binding was markedly decreased. Conclusions These studies demonstrate that Plg-R(KT) is required for plasminogen binding and macrophage migration in vivo. In addition, Plg-R(KT) deficiency is not compatible with survival of the species, due to the death of all offspring of Plg-R(KT)(-/-) females. This new mouse model will be important for future studies aimed at delineating the role of cell surface plasminogen activation in challenge and disease models in vivo.