title: Lack of both α2-antiplasmin and plasminogen activator inhibitor type-1 induces high IgE production.
abstract: OBJECTIVE
  We investigated the pathophysiological changes in mice lacking α2-antiplasmin (α2-AP) and plasminogen activator inhibitor type-1 (PAI-1) genes, and elucidated the involvement of these inhibitors for fibrinolysis in immune response.
  
  
  METHODS
  The pathophysiological changes induced by a lack of both α2-AP and PAI-1 were investigated using double knockout (KO) mice. The lung, liver, kidney and spleen tissues from α2-AP/PAI-1-double KO mice were compared with those from wild-type (WT) mice. Furthermore, the bone marrow cells from α2-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.
  
  
  RESULTS
  Plasma IgE levels in the α2-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 α2-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 α2-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 α2-AP/PAI-1-double KO mice.
  
  
  CONCLUSIONS
  The simultaneous expression of both the α2-AP and PAI-1 genes contributes to the maintenance of immunological functions that are related to IgE. Moreover, it is suggested that both α2-AP and PAI-1 are involved in the recruitment of lymphocytes in the peripheral tissues.
authors.affiliation: Department of Physiology, Kinki University, Faculty of Medicine, Osakasayama, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okada
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ueshima
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kawao
authors.forename: Masato
authors.initials: M
authors.lastname: Yano
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Tamura
authors.forename: Masaki
authors.initials: M
authors.lastname: Tanaka
authors.forename: Akemi
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
authors.forename: Masafumi
authors.initials: M
authors.lastname: Arima
authors.forename: Seiji
authors.initials: S
authors.lastname: Miyata
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nagai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
mesh_terms: D000367:Age Factors; D000818:Animals; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000097:blood; D005342:Fibrinolysis; D007073:Immunoglobulin E / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D000979:alpha-2-Antiplasmin / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; D007073:Immunoglobulin E
keywords: Bone marrow cells; Gene deficient mice; IgE regulation; PAI-1; α(2)-AP