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International Immunology Advance Access originally published online on July 14, 2006
International Immunology 2006 18(9):1355-1362; doi:10.1093/intimm/dxl068
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Modulation of matrix metalloproteinase-9 (MMP-9) secretion in B lymphopoiesis

Doron Melamed1,2,3, Orit Messika1,3,4, Lea Glass-Marmor4 and Ariel Miller1,2,4

1 Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
2 Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel
3 Department of Immunology, Technion, Haifa, Israel
4 Neuroimmunology Unit, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel

Correspondence to: A. Miller; E-mail: millera{at}tx.technion.ac.il

The matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the extracellular matrix, thus involved in cellular migration. The extent and role of MMPs secretion in primary non-transformed B cells, and specifically during early stages of development in the bone marrow (BM), has been barely unveiled. Herein, we investigated the secretion of MMP-9 during B lymphopoiesis and its modulation in response to different mitogens and cytokines. To do so, we used our BM culture system and well-studied mutated mouse models to isolate the different B cell populations. Our results show that MMP-9 is spontaneously secreted throughout B lymphopoiesis, and that the level of secreted MMP-9 is developmentally regulated. Using reverse transcription–PCR, we found that IFNßR is expressed throughout B cell development, while tumor necrosis factor (TNF)-{alpha}R-p55 and IFN{gamma}R expressions are initiated only at the pre-B stage. We found that TNF{alpha} stimulates MMP-9 secretion in transitional cells, whereas IFNs suppress MMP-9 secretion in immature cells. LPS and phorbol 12-myristate 13-acetate suppressed MMP-9 secretion in transitional cells, whereas LPS and concanavalin A stimulated MMP-9 secretion in mature B cells. We conclude that B lymphocyte development is accompanied with MMP-9 secretion and the developing cells are competent to modify this secretion upon different immune stimuli.

Keywords: autoimmune, B cells, cytokines, gelatinase, hematopoiesis, inflammation, migration

Transmitting editor: D. Wallach


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