Antigen-driven lymphocyte recruitment to the lung is diminished in the absence of urokinase-type plasminogen activator (uPA) receptor, but is independent of uPA.
The requirement for urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in T lymphocyte migration is unknown. uPA(-/-) mice have fewer pulmonary lymphocytes in response to certain infections, but its unknown whether this is due to diminished recruitment. Primed, recipient mice were IT inoculated with Ag. Three days later, fluorescently labeled lymphoblasts from background-matched control wild-type (WT), uPA(-/-), or uPAR(-/-) donor mice were injected i.v., and their recruitment was determined. Approximately twice the number of uPA(-/-) compared with WT lymphoblasts were recruited to the lungs of WT recipients. This difference was eliminated when uPA(-/-) and WT lymphoblasts were injected into uPA(-/-) recipients. Thus, the reduced number of lung lymphocytes in infected uPA(-/-) mice is not due to reduced recruitment. However, uPAR is critically involved in recruitment. Markedly fewer uPAR(-/-) compared with WT lymphoblasts were recruited to the lung. These findings suggest that uPAR may be a novel target for immune modulation in T lymphocyte-mediated disorders.
Gyetko
M R
MR
Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Ann Arbor Veterans Affairs Medical Center and University of Michigan Medical Center, Ann Arbor, MI 48109, USA. mgyetko@umich.edu
Sud
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Sonstein
J
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Polak
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Sud
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Curtis
J L
JL
D000818:Animals; D000941:Antigens / Q000276:immunology; D002465:Cell Movement; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D008168:Lung / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D013601:T-Lymphocytes / Q000276:immunology*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000502:physiology*
D000941:Antigens; D005452:Fluoresceins; D005456:Fluorescent Dyes; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C069306:5-chloromethylfluorescein; D014568:Urokinase-Type Plasminogen Activator