CD14(-BLOOD MONONUCLEAR-CELLS MIGRATE ACROSS ENDOTHELIUM AND GIVE RISE TO IMMUNOSTIMULATORY DENDRITIC CELLS()CD34(+) PERIPHERAL)

We describe a subset of peripheral CD14(+) cells, coexpressing the CD3 4 progenitor marker and able to migrate across endothelial cell monola yers, On culture with granulocyte-macrophage-CSF, this population diff erentiated into dendritic cells expressing CD83, CD80, HLA-DRbright, C D86, and CD54, These dendritic cells were immunostimulatory, in that t hey induced proliferation of allogenic and tetanus toxoid-specific T l ymphocytes. The CD14(+)CD34(+) population expressed higher levels of p latelet endothelial cell adhesion molecule-1 (PECAM-1) and alpha(4) be ta(1) integrin than the CD14(+)CD34(-) counterpart, being dull positiv e for other integrins, Using stably transfected PECAM-1(+), VCAM-1(+), or ICAM-1(+) cells, we found that PECAM-1 and, to a lesser extent, VC AM-1, could support transmigration of CD14(+)CD34(+) cells, whereas th e alpha L-ICAM-1 interaction was involved in cell adhesion, PECAM-1-dr iven transmigration was conceivably dependent on a haptotactic gradien t, as it was reduced by 80% across NIH/3T3 cells transfected with the PECAM-1-Delta cyto deletion mutant, This mutant lacks the cytoplasmic tail and displays a reduced tendency to localize at the intercellular junctions, thus failing to form a molecular junctional gradient, Once differentiated, dendritic cells derived from CD14(+)CD34(+) precursors retained their transendothelial migratory capability, using both PECA M-1 and ICAM-1 for transmigration, We suggest that a subset of CD14(+) CD34(+) circulating leukocytes can localize to peripheral tissues and differentiate into functional dendritic cells, thus representing a fun ctional reservoir of potential APC, PECAM-1, constitutively expressed on vascular endothelium, is likely to play a relevant role in the egre ss of this population from the bloodstream.