uPA/uPAR system is active in immature dendritic cells derived from CD14+CD34+ precursors and is down-regulated upon maturation

Elisabetta Ferrero, Katuscia Vettoretto, Attilio Bondanza, Antonello Villa, Massimo Resnati, Alessandro Poggi, Maria Raffaella Zocchi

Research output: Contribution to journalArticle

Abstract

We recently described a subset of peripheral CD14+CD34+ cells able to migrate across endothelial cell monolayers and differentiate into immunostimulatory dendritic cells (DC). In this paper we show that immature DC derived from CD14+CD34+ precursors are also capable of reverse transendothelial migration and extracellular matrix (ECM) invasion using the urokinase plasminogen activator receptor (uPAR). We found that these cells respond to macrophage-inflammatory protein (MIP)-1α, enhancing their ability to invade ECM and supporting the idea that immature DC are selectively recruited at the site of inflammation to expand the pool of APCs. Interestingly, MIP-1α was also capable of preventing the decreased matrix invasion observed by blocking uPAR, suggesting that the uPA/uPAR system and MIP-1α cooperate in driving immature DC migration through the subendothelial matrix. Upon exposure to maturating stimuli, such as TNF-α, CD14+CD34+- derived DC enhance their APC function and decrease the capacity of invading ECM; these changes are accompanied by altered expression and function of uPAR. Moreover, mature DC shift their sensitivity from MIP-1α to MIP-3β, enhancing their transendothelial migration capability in response to the latter chemokine. Our data support the hypothesis that bloodborne DC can move through ECM toward the site of pathogen entry where they differentiate into fully mature APCs with their motility and function regulated by microenvironmental stimuli, including MIP-1α, MIP-3β, and TNF-α.

Original languageEnglish
Pages (from-to)712-718
Number of pages7
JournalJournal of Immunology
Volume164
Issue number2
Publication statusPublished - Jan 15 2000

ASJC Scopus subject areas

  • Immunology

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