CD14+ CD34+ peripheral blood mononuclear cells migrate across endothelium and give rise to immunostimulatory dendritic cells.
We describe a subset of peripheral CD14+ cells, coexpressing the CD34 progenitor marker and able to migrate across endothelial cell monolayers. On culture with granulocyte-macrophage-CSF, this population differentiated into dendritic cells expressing CD83, CD80, HLA-DR(bright), CD86, and CD54. These dendritic cells were immunostimulatory, in that they induced proliferation of allogenic and tetanus toxoid-specific T lymphocytes. The CD14+ CD34+ population expressed higher levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and alpha4beta1 integrin than the CD14+ CD34- counterpart, being dull positive for other integrins. Using stably transfected PECAM-1+, VCAM-1+, or ICAM-1+ cells, we found that PECAM-1 and, to a lesser extent, VCAM-1, could support transmigration of CD14+ CD34+ cells, whereas the alphaL-ICAM-1 interaction was involved in cell adhesion. PECAM-1-driven transmigration was conceivably dependent on a haptotactic gradient, as it was reduced by 80% across NIH3T3 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 PECAM-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 functional reservoir of potential APC. PECAM-1, constitutively expressed on vascular endothelium, is likely to play a relevant role in the egress of this population from the bloodstream.
Ferrero
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E
Laboratory of Tumor Immunology, Scientific Institute San Raffaele, Milan, Italy.
Bondanza
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A
Leone
B E
BE
Manici
S
S
Poggi
A
A
Zocchi
M R
MR
D018952:Antigens, CD34 / Q000032:analysis*; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis
D018952:Antigens, CD34; D018950:Lipopolysaccharide Receptors; D019408:Platelet Endothelial Cell Adhesion Molecule-1