Lack of both α2-antiplasmin and plasminogen activator inhibitor type-1 induces high IgE production.

Abstract Aims We investigated the pathophysiological changes in mice lacking α 2 -antiplasmin (α 2 -AP) and plasminogen activator inhibitor type-1 (PAI-1) genes, and elucidated the involvement of these inhibitors for fibrinolysis in immune response. Main methods The pathophysiological changes induced by a lack of both α 2 -AP and PAI-1 were investigated using double knockout (KO) mice. The lung, liver, kidney and spleen tissues from α 2 -AP/PAI-1-double KO mice were compared with those from wild-type (WT) mice. Furthermore, the bone marrow cells from α 2 -AP/PAI-1-double KO mice were transplanted into 10-Gy X ray irradiated WT mice, and then the effects of the transplantation were studied. Key findings Plasma IgE levels in the α 2 -AP/PAI-1-double KO mice increased with age and exceeded 1000 ng/mL after 6 months of age. The plasma cells that produced IgE were detected in perivascular assembled lymphocytes. In the α 2 -AP/PAI-1-double KO mice, perivascular lymphocyte infiltration was observed in the lung, liver, and kidneys and peribronchial lymphocyte infiltration was present in the lung. When the bone marrow cells from α 2 -AP/PAI-1-double KO mice were transplanted into 10-Gy X ray irradiated WT mice, the phenotypes of the recipients were similar to those of α 2 -AP/PAI-1-double KO mice. Significance The simultaneous expression of both the α 2 -AP and PAI-1 genes contributes to the maintenance of immunological functions that are related to IgE. Moreover, it is suggested that both α 2 -AP and PAI-1 are involved in the recruitment of lymphocytes in the peripheral tissues.