Modulation of matrix metalloproteinase-9 (MMP-9) secretion in B lymphopoiesis.
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 IFNbetaR is expressed throughout B cell development, while tumor necrosis factor (TNF)-alphaR-p55 and IFNgammaR expressions are initiated only at the pre-B stage. We found that TNFalpha 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.
Melamed
Doron
D
Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Messika
Orit
O
Glass-Marmor
Lea
L
Miller
Ariel
A
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation; D007107:Immune System / Q000254:growth & development*; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism; D038041:Lymphopoiesis / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D017471:Receptors, Interferon / Q000276:immunology / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000201:enzymology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D000096743:Interferon gamma Receptor
D016899:Interferon-beta; D020780:Matrix Metalloproteinase 9; D017471:Receptors, Interferon; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor