A family with Papillon-Lefevre syndrome reveals a requirement for cathepsin C in granzyme B activation and NK cell cytolytic activity.
Blood
; 107(9): 3665-8, 2006 May 01.
Article
em En
| MEDLINE
| ID: mdl-16410452
ABSTRACT
Activation of granzyme B, a key cytolytic effector molecule of natural killer (NK) cells, requires removal of an N-terminal pro-domain. In mice, cathepsin C is required for granzyme processing and normal NK cell cytolytic function, whereas in patients with Papillon-Lefèvre syndrome (PLS), loss-of-function mutations in cathepsin C do not affect lymphokine activated killer (LAK) cell function. Here we demonstrate that resting PLS NK cells do have a cytolytic defect and fail to induce the caspase cascade in target cells. NK cells from these patients contain inactive granzyme B, indicating that cathepsin C is required for granzyme B activation in unstimulated human NK cells. However, in vitro activation of PLS NK cells with interleukin-2 restores cytolytic function and granzyme B activity by a cathepsin C-independent mechanism. This is the first documented example of a human mutation affecting granzyme B activity and highlights the importance of cathepsin C in human NK cell function.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Doença de Papillon-Lefevre
/
Serina Endopeptidases
/
Células Matadoras Naturais
/
Catepsina C
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Blood
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Reino Unido