International Immunology Advance Access published online on July 14, 2006
International Immunology, doi:10.1093/intimm/dxl068
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1 Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel; Department of Immunology, Technion, Haifa, Israel
* To whom correspondence should be addressed. 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 IFN
Received March 2, 2006
Accepted June 16, 2006
Article
Modulation of matrix metalloproteinase-9 (MMP-9) secretion in B lymphopoiesis
Doron Melamed 1,
Orit Messika 2,
Lea Glass-Marmor 3,
and
Ariel Miller 4 *
2 Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Department of Immunology, Technion, Haifa, Israel; Neuroimmunology Unit, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel
3 Neuroimmunology Unit, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel
4 Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel; Neuroimmunology Unit, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel
Ariel Miller, E-mail: millera{at}tx.technion.ac.il
Abstract 
R is expressed throughout B cell development, while tumor necrosis factor (TNF)-
R-p55 and IFN
R expressions are initiated only at the pre-B stage. We found that TNF 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.
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