PMID- 14688127
OWN - NLM
STAT- MEDLINE
DCOM- 20040202
LR  - 20210526
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 72
IP  - 1
DP  - 2004 Jan
TI  - Urokinase-deficient mice fail to generate a type 2 immune response following 
      schistosomal antigen challenge.
PG  - 461-7
AB  - Activated lymphocytes express urokinase-type plasminogen activator (uPA). 
      Previous work suggests that uPA modulates T-lymphocyte responses. Mice deficient 
      in uPA (uPA(-/-)) fail to generate type 1 (T1) immune responses during infection 
      with Cryptococcus neoformans. Failure to generate either a T1 or a T2 immune 
      response is not predictive of defects in the alternative response. Conversely, 
      down-regulation of one type of immune response may result in inappropriate 
      overactivation of the other. It is not known whether the immune defect in 
      uPA(-/-) mice affects only T1 responses or whether T2 responses are also 
      impaired. Impairment of both T1 and T2 responses would suggest a global T-cell 
      defect in the absence of uPA. To determine the role of uPA in T2 immune 
      responses, wild-type (WT) and uPA(-/-) mice were primed and challenged with 
      schistosomal egg antigen (SEA). This elicits strong polarization to T2 immune 
      responses in immunocompetent mice. The challenged WT mice developed delayed-type 
      hypersensitivity (DTH) to SEA; high levels of serum immunoglobulin E (IgE); a 
      strong T2 cytokine phenotype with markedly elevated levels of interleukin-4 
      (IL-4), IL-5, and IL-13; and eosinophil-rich pulmonary granulomas. uPA(-/-) mice 
      failed to develop DTH to SEA; did not polarize Ig production to IgE; did not 
      produce high levels of IL-4, IL-5, or IL-13; and had markedly reduced numbers of 
      granuloma-associated eosinophils. uPA(-/-) mice fail to generate polarized T2 
      immune responses to a T2-inducing pathogen. These findings, in conjunction with 
      our previous work, demonstrate that mice deficient in uPA have profoundly 
      impaired immunity involving both T1 and T2 polarization and are largely 
      immunologically unresponsive.
FAU - Gyetko, Margaret R
AU  - Gyetko MR
AD  - Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, 
      Veterans Affairs Ann Arbor Healthcare System and University of Michigan Medical 
      Center, Ann Arbor, Michigan 48109, USA. mgyetko@umich.edu
FAU - Sud, Sudha
AU  - Sud S
FAU - Chensue, Stephen W
AU  - Chensue SW
LA  - eng
GR  - HL60620/HL/NHLBI NIH HHS/United States
GR  - N01-AI-55270/AI/NIAID NIH HHS/United States
GR  - R01 HL060620/HL/NHLBI NIH HHS/United States
GR  - R03 AI055270/AI/NIAID NIH HHS/United States
GR  - AI43460/AI/NIAID NIH HHS/United States
GR  - R01 AI043460/AI/NIAID NIH HHS/United States
GR  - R56 AI043460/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antigens, Helminth)
RN  - 0 (Cytokines)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Antigens, Helminth/*immunology
MH  - Cytokines/biosynthesis
MH  - Granuloma, Respiratory Tract/immunology
MH  - Hypersensitivity, Delayed/etiology
MH  - Immunoglobulin E/blood
MH  - Lymphocyte Activation
MH  - Mice
MH  - Schistosoma/*immunology
MH  - Schistosomiasis/immunology
MH  - T-Lymphocytes/immunology
MH  - Th2 Cells/*immunology
MH  - Urokinase-Type Plasminogen Activator/deficiency/*metabolism
PMC - PMC343962
EDAT- 2003/12/23 05:00
MHDA- 2004/02/03 05:00
PMCR- 2004/01/01
CRDT- 2003/12/23 05:00
PHST- 2003/12/23 05:00 [pubmed]
PHST- 2004/02/03 05:00 [medline]
PHST- 2003/12/23 05:00 [entrez]
PHST- 2004/01/01 00:00 [pmc-release]
AID - 0744 [pii]
AID - 10.1128/IAI.72.1.461-467.2004 [doi]
PST - ppublish
SO  - Infect Immun. 2004 Jan;72(1):461-7. doi: 10.1128/IAI.72.1.461-467.2004.