Plasminogen promotes macrophage phagocytosis in mice

• Published in: Blood 2014-07, Vol.124 (5), p.679-688
• Main Authors: Das, Riku, Ganapathy, Swetha, Settle, Megan, Plow, Edward F.
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Down-Regulation; Immunity, Innate; Kupffer Cells - cytology; Kupffer Cells - immunology; Kupffer Cells - metabolism; Macrophages, Peritoneal - cytology; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Mice; Mice, Knockout; Phagocytosis - physiology; Plasminogen - genetics; Plasminogen - immunology; Plasminogen - metabolism; Plenary Paper; Receptors, Cell Surface - biosynthesis; Receptors, Cell Surface - genetics; Receptors, Cell Surface - immunology; Spleen
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2014-01-549659

The phagocytic function of macrophages plays a pivotal role in eliminating apoptotic cells and invading pathogens. Evidence implicating plasminogen (Plg), the zymogen of plasmin, in phagocytosis is extremely limited with the most recent in vitro study showing that plasmin acts on prey cells rather than on macrophages. Here, we use apoptotic thymocytes and immunoglobulin opsonized bodies to show that Plg exerts a profound effect on macrophage-mediated phagocytosis in vitro and in vivo. Plg enhanced the uptake of these prey by J774A.1 macrophage-like cells by 3.5- to fivefold Plg receptors and plasmin proteolytic activity were required for phagocytosis of both preys. Compared with Plg+/+ mice, Plg−/− mice exhibited a 60% delay in clearance of apoptotic thymocytes by spleen and an 85% reduction in uptake by peritoneal macrophages. Phagocytosis of antibody-mediated erythrocyte clearance by liver Kupffer cells was reduced by 90% in Plg−/− mice compared with Plg+/+ mice. A gene array of splenic and hepatic tissues from Plg−/− and Plg+/+ mice showed downregulation of numerous genes in Plg−/− mice involved in phagocytosis and regulation of phagocytic gene expression was confirmed in macrophage-like cells. Thus, Plg may play an important role in innate immunity by changing expression of genes that contribute to phagocytosis. •Plasminogen influences uptake of apoptotic bodies and immunoglobulin-coated red cells by macrophages in mice.•Plasminogen regulates expression of genes involved in macrophage phagocytosis in vivo.