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*
Laboratory of Tumor Immunology and
Department of Biology and Biotechnology, San Raffaele Scientific Institute, Milan, Italy;
Department of Pharmacology, Consiglio Nazionale delle Ricerche Cytopharmacology, and B. Ceccarelli Centers, Milan, Italy; and
Laboratory of Immunopathology, National Institute for Cancer Research and Advanced Biotechnology Center, Genoa, Italy
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)-1
, 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-1 was
also capable of preventing the decreased matrix invasion observed by
blocking uPAR, suggesting that the uPA/uPAR system and MIP-1
cooperate in driving immature DC migration through the subendothelial
matrix. Upon exposure to maturating stimuli, such as TNF-,
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-1 to MIP-3
, 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-1, MIP-3, and
TNF-.
This article has been cited by other articles:
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  D. Ilkovitch and D. M. Lopez Urokinase-mediated recruitment of myeloid-derived suppressor cells and their suppressive mechanisms are blocked by MUC1/sec Blood, May 7, 2009; 113(19): 4729 - 4739. [Abstract] [Full Text] [PDF]
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 D. Ilkovitch, M. E. Handel-Fernandez, L. M. Herbert, and D. M. Lopez Antitumor Effects of Mucin 1/sec Involves the Modulation of Urokinase-Type Plasminogen Activator and Signal Transducer and Activator of Transcription 1 Expression in Tumor Cells Cancer Res., April 1, 2008; 68(7): 2427 - 2435. [Abstract] [Full Text] [PDF]
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 V. Chabot, P. Reverdiau, S. Iochmann, A. Rico, D. Senecal, C. Goupille, P.-Y. Sizaret, and L. Sensebe CCL5-enhanced human immature dendritic cell migration through the basement membrane in vitro depends on matrix metalloproteinase-9 J. Leukoc. Biol., April 1, 2006; 79(4): 767 - 778. [Abstract] [Full Text] [PDF]
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M. Alfano, N. Sidenius, F. Blasi, and G. Poli The role of urokinase-type plasminogen activator (uPA)/uPA receptor in HIV-1 infection J. Leukoc. Biol., November 1, 2003; 74(5): 750 - 756. [Abstract] [Full Text] [PDF]
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E. Ferrero, D. Belloni, P. Contini, C. Foglieni, M. E. Ferrero, M. Fabbri, A. Poggi, and M. R. Zocchi Transendothelial migration leads to protection from starvation-induced apoptosis in CD34+CD14+ circulating precursors: evidence for PECAM-1 involvement through Akt/PKB activation Blood, January 1, 2003; 101(1): 186 - 193. [Abstract] [Full Text] [PDF]
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 M. Alfano, N. Sidenius, B. Panzeri, F. Blasi, and G. Poli Urokinase-urokinase receptor interaction mediates an inhibitory signal for HIV-1 replication PNAS, June 25, 2002; 99(13): 8862 - 8867. [Abstract] [Full Text] [PDF]
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 Y. Wei, J. A. Eble, Z. Wang, J. A. Kreidberg, and H. A. Chapman Urokinase Receptors Promote beta 1 Integrin Function through Interactions with Integrin alpha 3beta 1 Mol. Biol. Cell, October 1, 2001; 12(10): 2975 - 2986. [Abstract] [Full Text] [PDF]
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E. Grage-Griebenow, H.-D. Flad, and M. Ernst Heterogeneity of human peripheral blood monocyte subsets J. Leukoc. Biol., January 1, 2001; 69(1): 11 - 20. [Abstract] [Full Text]
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