INVESTIGADORES
CHULUYAN Hector Eduardo
artículos
Título:
Neutrophil elastase converts human immature dendritic cells into transforming growth factor-beta1-secreting cells and reduces allostimulatory ability.
Autor/es:
MAFFIA PC, ZITTERMANN SE, SCIMONE ML, TATEOSIAN N, AMIANO N, GUERRIERI D, LUTZKY V, ROSSO D, ROMEO HE, GARCIA VE, ISSEKUTZ AC, CHULUYAN HE.
Revista:
AMERICAN JOURNAL OF PATHOLOGY
Referencias:
Lugar: Maryland; Año: 2007 vol. 171 p. 928 - 937
ISSN:
0002-9440
Resumen:
During microbial infection, neutrophils (polymorphonuclear leukocytes;
PMNs) activate dendritic cells (DCs). However, early reports
illustrated that neutrophil-derived mediators may suppress responses to
mitogens. In the present study, we investigated the mechanism used by
PMNs to modulate the immunostimulatory ability of DCs. Autologous
syngeneic PMNs decreased T-cell proliferation induced by allogeneic
DCs. Culture supernatant (CS) derived from PMNs also decreased
allostimulation ability of immature DCs and increased the expression of
transforming growth factor (TGF)-beta1 on DCs. A TGF-beta1 monoclonal
antibody, a CD40 monoclonal antibody, or a serine protease inhibitor
reversed the effect of PMN CS on DC allostimulatory ability.
Furthermore, elastase reproduced the inhibitory effect of PMN CS on DC
allostimulatory ability and the TGF-beta1 production. The role of
elastase was confirmed by examining PMN CS from two patients with
cyclic neutropenia, a disease due to mutations in the neutrophil
elastase gene. These PMN CS samples had reduced elastase activity and
were unable to increase DC TGF-beta1 production. Moreover, elastase and
PMN CS induced IkappaBalpha degradation in DCs. We conclude that PMNs
decrease DC allostimulatory ability via production of elastase leading
to a switch of immature DCs into TGF-beta1-secreting cells.