Recruitment of polymorphonuclear leukocytes by dendritic cells.

SCIMONE ML, LUTZKY V, ZITTERMANN S, MAFFIA P, JANCIC C, CHULUYAN HE.

IMMUNOLOGY

Año: 2005 vol. 114 p. 375 - 385

0019-2805

ABSTRACT Dendritic cells (DCs) are the most potent antigen-presenting cells and populate many tissues, where they may participate in inflammatory reactions.  Polymorphonuclear leukocye (PMNL) infiltration into tissues is a prominent feature of inflammation.  The mechanisms of PMNL recruitment depend on chemotactic factors and adhesion molecules expressed on endothelial cells.  The aim of the present study was to determinate whether DCs participate in the early recruitment of PMNLs.  DCs derived from peripheral blood monocytes with IL-4+GM-CSF were used for this study.  PMNLs incubated with culture supernatant (CS) from untreated or TNFa-treated (1 h, 100 U/ml, 37°C) monocyte derived DCs (moDCs) increased the expression on PMNL of both CD11b and CD18 (22% and 6% increase, respectively).  Both untreated and TNFa-treated moDCs induced the chemotaxis of PMNLs (23.9 ± 11.8% and 21.4 ± 8.6%, respectively; n = 10).  Blocking experiments with mAbs to CXCL8, CXCL5, CXCL7 and Pan GRO (CXCL1, CXCL2, CXCL3) suggested that CXCL8/IL-8 was the chemokine responsible for the PMNL chemotactic activity in the CS of untreated and TNFa-treated moDC.  However, the level of CXCL8 in CS from TNFa-treated moDCs was twice that in untreated moDCs.  The regulation of CXCL8 production in moDCs by adhesion molecule engagement was examined.  Adhesion of immature moDCs to endothelium involved CD31, CD18, CD29 and CD49d.  Engagement of domain 2-3 of CD31, but not of CD29 or CD18, decreased the production of CXCL8 by immature but not by mature moDCs, which have lower levels of CD31 than immature moDCs.  Overall, these results suggest that DCs not only trigger a specific immune response, but also the innate immune response by recruiting PMNLs.  Furthermore, CXCL8 production by immature DCs is regulated by CD31 signalling, perhaps during their migration through vascular endothelium.