S Okada, H Kita, TJ George, GJ Gleich and KM Leiferman
Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.

In general, inflammatory cells cross basement membranes by producing proteinases. To investigate the role of proteinases in eosinophil basement membrane migration, we studied peripheral blood eosinophils in Matrigel-coated chemotaxis chambers. Electron microscopy showed degradation of the Matrigel layer when eosinophils, added to the upper chamber, transmigrated the membrane in the presence of both platelet- activating factor (PAF) in the lower chamber and interleukin (IL)-5 in both chambers. In the absence of either or both PAF and IL-5, no changes occurred in the Matrigel layer. Matrigel transmigration of eosinophils induced by PAF and IL-5 was inhibited by 1,10- phenanthroline, batimastat, 3,4-dichloroisocoumarin, chymostatin, and a neutralizing antibody for the matrix metalloproteinase (MMP)-9, indicating that serine proteinase(s) and MMP, specifically MMP-9, were involved in the transmigration of eosinophils through Matrigel. In contrast, eosinophil migration through a bare membrane was not affected by batimastat. Using gelatin zymography and immunoblotting, MMP-9 was detected in the migration upper chamber supernatant of the eosinophil transmigration assay and in the conditioned medium of eosinophils. Release of MMP-9 by eosinophils was increased by IL-5, PAF, or both, but the substrate-degrading activity of MMP-9 was increased only in the presence of both IL-5 and PAF, indicating that the releasing and activating mechanisms of MMP-9 are involved in eosinophil basement membrane migration. This study implicates MMP-9 in basement membrane migration of eosinophils and suggests its involvement in inflammatory diseases where tissue eosinophilia plays a role.

This article has been cited by other articles:

				W. J. Lubbe, D. S. Zuzga, Z. Zhou, W. Fu, J. Pelta-Heller, R. J. Muschel, S. A. Waldman, and G. M. Pitari Guanylyl Cyclase C Prevents Colon Cancer Metastasis by Regulating Tumor Epithelial Cell Matrix Metalloproteinase-9 Cancer Res., April 15, 2009; 69(8): 3529 - 3536. [Abstract] [Full Text] [PDF]

				A. Langlois, F. Chouinard, N. Flamand, C. Ferland, M. Rola-Pleszczynski, and M. Laviolette Crucial implication of protein kinase C (PKC)-{delta}, PKC-{zeta}, ERK-1/2, and p38 MAPK in migration of human asthmatic eosinophils J. Leukoc. Biol., April 1, 2009; 85(4): 656 - 663. [Abstract] [Full Text] [PDF]

				C. Tefe-Silva, D. I. Souza, M. T. Ueta, E. M. Floriano, L. H. Faccioli, and S. G. Ramos Interference of Dexamethasone in the Pulmonary Cycle of Strongyloides venezuelensis in Rats Am J Trop Med Hyg, October 1, 2008; 79(4): 571 - 578. [Abstract] [Full Text] [PDF]

				A.H. Nissim Ben Efraim and F. Levi-Schaffer Review: Tissue remodeling and angiogenesis in asthma: the role of the eosinophil Therapeutic Advances in Respiratory Disease, June 1, 2008; 2(3): 163 - 171. [Abstract] [PDF]

				M. Abel and H. Vliagoftis Mast Cell-Fibroblast Interactions Induce Matrix Metalloproteinase-9 Release from Fibroblasts: Role for IgE-Mediated Mast Cell Activation J. Immunol., March 1, 2008; 180(5): 3543 - 3550. [Abstract] [Full Text] [PDF]

				F. Taheri and H. E. P. Bazan Platelet-Activating Factor Overturns the Transcriptional Repressor Disposition of Sp1 in the Expression of MMP-9 in Human Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 1931 - 1941. [Abstract] [Full Text] [PDF]

				P Boschetto, S Quintavalle, E Zeni, S Leprotti, A Potena, L Ballerin, A Papi, G Palladini, M Luisetti, L Annovazzi, et al. Association between markers of emphysema and more severe chronic obstructive pulmonary disease Thorax, December 1, 2006; 61(12): 1037 - 1042. [Abstract] [Full Text] [PDF]

				M. Suzukawa, A. Komiya, M. Iikura, H. Nagase, C. Yoshimura-Uchiyama, H. Yamada, H. Kawasaki, K. Ohta, K. Matsushima, K. Hirai, et al. Trans-basement membrane migration of human basophils: role of matrix metalloproteinase-9 Int. Immunol., November 1, 2006; 18(11): 1575 - 1583. [Abstract] [Full Text] [PDF]

				N. Di Girolamo, I. Indoh, N. Jackson, D. Wakefield, H. P. McNeil, W. Yan, C. Geczy, J. P. Arm, and N. Tedla Human Mast Cell-Derived Gelatinase B (Matrix Metalloproteinase-9) Is Regulated by Inflammatory Cytokines: Role in Cell Migration J. Immunol., August 15, 2006; 177(4): 2638 - 2650. [Abstract] [Full Text] [PDF]

				D. H. Lim, J. Y. Cho, M. Miller, K. McElwain, S. McElwain, and D. H. Broide Reduced peribronchial fibrosis in allergen-challenged MMP-9-deficient mice. Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L265 - L271. [Abstract] [Full Text] [PDF]

				K. S. Lee, K. H. Min, S. R. Kim, S. J. Park, H. S. Park, G. Y. Jin, and Y. C. Lee Vascular Endothelial Growth Factor Modulates Matrix Metalloproteinase-9 Expression in Asthma Am. J. Respir. Crit. Care Med., July 15, 2006; 174(2): 161 - 170. [Abstract] [Full Text] [PDF]

				J. J. Atkinson and S. D. Shapiro Neutrophil-mediated eosinophil transmigration: parting the red sea or leaving bread crumbs. Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 645 - 646. [Full Text] [PDF]

				A. G. Braundmeier, A. T. Fazleabas, B. A. Lessey, H. Guo, B. P. Toole, and R. A. Nowak Extracellular Matrix Metalloproteinase Inducer Regulates Metalloproteinases in Human Uterine Endometrium J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2358 - 2365. [Abstract] [Full Text] [PDF]

				I. Kikuchi, S. Kikuchi, T. Kobayashi, K. Hagiwara, Y. Sakamoto, M. Kanazawa, and M. Nagata Eosinophil Trans-Basement Membrane Migration Induced by Interleukin-8 and Neutrophils Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 760 - 765. [Abstract] [Full Text] [PDF]

				C. C. Taggart, C. M. Greene, T. P. Carroll, S. J. O'Neill, and N. G. McElvaney Elastolytic Proteases: Inflammation Resolution and Dysregulation in Chronic Infective Lung Disease Am. J. Respir. Crit. Care Med., May 15, 2005; 171(10): 1070 - 1076. [Full Text] [PDF]

				A. Leonardi, P. Brun, M. T. Sartori, R. Cortivo, C. DeDominicis, G. Saggiorato, G. Abatangelo, and A. G. Secchi Urokinase Plasminogen Activator, uPa Receptor, and Its Inhibitor in Vernal Keratoconjunctivitis Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1364 - 1370. [Abstract] [Full Text] [PDF]

				H Matsumoto, A Niimi, M Takemura, T Ueda, M Minakuchi, R Tabuena, K Chin, T Mio, Y Ito, S Muro, et al. Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma Thorax, April 1, 2005; 60(4): 277 - 281. [Abstract] [Full Text] [PDF]

				C. Ferland, N. Flamand, F. Davoine, J. Chakir, and M. Laviolette IL-16 Activates Plasminogen-Plasmin System and Promotes Human Eosinophil Migration into Extracellular Matrix via CCR3-Chemokine-Mediated Signaling and by Modulating CD4 Eosinophil Expression J. Immunol., October 1, 2004; 173(7): 4417 - 4424. [Abstract] [Full Text] [PDF]

				M. A. Pouladi, C. S. Robbins, F. K. Swirski, M. Cundall, A. N.J. McKenzie, M. Jordana, S. D. Shapiro, and M. R. Stampfli Interleukin-13-Dependent Expression of Matrix Metalloproteinase-12 Is Required for the Development of Airway Eosinophilia in Mice Am. J. Respir. Cell Mol. Biol., January 1, 2004; 30(1): 84 - 90. [Abstract] [Full Text] [PDF]

				N. G. Sandler, M. M. Mentink-Kane, A. W. Cheever, and T. A. Wynn Global Gene Expression Profiles During Acute Pathogen-Induced Pulmonary Inflammation Reveal Divergent Roles for Th1 and Th2 Responses in Tissue Repair J. Immunol., October 1, 2003; 171(7): 3655 - 3667. [Abstract] [Full Text] [PDF]

				Y Oshita, T Koga, T Kamimura, K Matsuo, T Rikimaru, and H Aizawa Increased circulating 92 kDa matrix metalloproteinase (MMP-9) activity in exacerbations of asthma Thorax, September 1, 2003; 58(9): 757 - 760. [Abstract] [Full Text] [PDF]

				A. Leonardi, P. Brun, G. Abatangelo, M. Plebani, and A. G. Secchi Tear Levels and Activity of Matrix Metalloproteinase (MMP)-1 and MMP-9 in Vernal Keratoconjunctivitis Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 3052 - 3058. [Abstract] [Full Text] [PDF]

				J. J. Atkinson and R. M. Senior Matrix Metalloproteinase-9 in Lung Remodeling Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 12 - 24. [Abstract] [Full Text] [PDF]

				L. Y. Liu, J. B. Sedgwick, M. E. Bates, R. F. Vrtis, J. E. Gern, H. Kita, N. N. Jarjour, W. W. Busse, and E. A. B. Kelly Decreased Expression of Membrane IL-5 Receptor {alpha} on Human Eosinophils: II. IL-5 Down-Modulates Its Receptor Via a Proteinase-Mediated Process J. Immunol., December 1, 2002; 169(11): 6459 - 6466. [Abstract] [Full Text] [PDF]

				W. Mattos, S. Lim, R. Russell, A. Jatakanon, K. F. Chung, and P. J. Barnes Matrix Metalloproteinase-9 Expression in Asthma: Effect of Asthma Severity, Allergen Challenge, and Inhaled Corticosteroids Chest, November 1, 2002; 122(5): 1543 - 1552. [Abstract] [Full Text] [PDF]

				K. H. Choi, H. B. Lee, M. Y. Jeong, Y. K. Rhee, M. J. Chung, Y. G. Kwak, and Y. C. Lee The Role of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Cryptogenic Organizing Pneumonia* Chest, May 1, 2002; 121(5): 1478 - 1485. [Abstract] [Full Text] [PDF]

				B. Vaillant, M. G. Chiaramonte, A. W. Cheever, P. D. Soloway, and T. A. Wynn Regulation of Hepatic Fibrosis and Extracellular Matrix Genes by the Th Response: New Insight into the Role of Tissue Inhibitors of Matrix Metalloproteinases J. Immunol., December 15, 2001; 167(12): 7017 - 7026. [Abstract] [Full Text] [PDF]

				A. M. Abu El-Asrar, I. Van Aelst, S. Al-Mansouri, L. Missotten, G. Opdenakker, and K. Geboes Gelatinase B in Vernal Keratoconjunctivitis Arch Ophthalmol, October 1, 2001; 119(10): 1505 - 1511. [Abstract] [Full Text] [PDF]

				R. L. Warner, C. S. Lewis, L. Beltran, E. M. Younkin, J. Varani, and K. J. Johnson The Role of Metalloelastase in Immune Complex-Induced Acute Lung Injury Am. J. Pathol., June 1, 2001; 158(6): 2139 - 2144. [Abstract] [Full Text] [PDF]

				C. Ferland, M. Guilbert, F. Davoine, N. Flamand, J. Chakir, and M. Laviolette Eotaxin promotes eosinophil transmigration via the activation of the plasminogen-plasmin system J. Leukoc. Biol., May 1, 2001; 69(5): 772 - 778. [Abstract] [Full Text]

				W. J. Howat, J. A. Holmes, S. T. Holgate, and P. M. Lackie Basement Membrane Pores in Human Bronchial Epithelium : A Conduit for Infiltrating Cells? Am. J. Pathol., February 1, 2001; 158(2): 673 - 680. [Abstract] [Full Text] [PDF]

				W. J. Lane, S. Dias, K. Hattori, B. Heissig, M. Choy, S. Y. Rabbany, J. Wood, M. A. S. Moore, and S. Rafii Stromal-derived factor 1-induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases Blood, December 15, 2000; 96(13): 4152 - 4159. [Abstract] [Full Text] [PDF]

				E. A. BECKY KELLY, W. W. BUSSE, and N. N. JARJOUR Increased Matrix Metalloproteinase-9 in the Airway after Allergen Challenge Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): 1157 - 1161. [Abstract] [Full Text]

				S. Ali, J. Kaur, and K. D. Patel Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Regulated on Activation Normal T Cell Expressed and Secreted Are Expressed by Human Breast Carcinoma Cells and Support Eosinophil Adhesion and Activation Am. J. Pathol., July 1, 2000; 157(1): 313 - 321. [Abstract] [Full Text] [PDF]

				A. Tanaka, K. Arai, Y. Kitamura, and H. Matsuda Matrix Metalloproteinase-9 Production, a Newly Identified Function of Mast Cell Progenitors, Is Downregulated by c-kit Receptor Activation Blood, October 1, 1999; 94(7): 2390 - 2395. [Abstract] [Full Text] [PDF]

				F. Levi-Schaffer, E. Garbuzenko, A. Rubin, R. Reich, D. Pickholz, P. Gillery, H. Emonard, A. Nagler, and F. A. X. Maquart Human eosinophils regulate human lung- and skin-derived fibroblast properties in vitro: A role for transforming growth factor beta (TGF-beta ) PNAS, August 17, 1999; 96(17): 9660 - 9665. [Abstract] [Full Text] [PDF]

				M. Guilbert, C. Ferland, M. Bosse, N. Flamand, S. Lavigne, and M. Laviolette 5-Oxo-6,8,11,14-Eicosatetraenoic Acid Induces Important Eosinophil Transmigration through Basement Membrane Components . Comparison of Normal and Asthmatic Eosinophils Am. J. Respir. Cell Mol. Biol., July 1, 1999; 21(1): 97 - 104. [Abstract] [Full Text]

				G. Mautino, C. Henriquet, D. Jaffuel, J. Bousquet, and F. Capony Tissue Inhibitor of Metalloproteinase-1 Levels in Bronchoalveolar Lavage Fluid from Asthmatic Subjects Am. J. Respir. Crit. Care Med., July 1, 1999; 160(1): 324 - 330. [Abstract] [Full Text]

				B. Dahlen, J. Shute, and P. Howarth Immunohistochemical localisation of the matrix metalloproteinases MMP-3 and MMP-9 within the airways in asthma Thorax, July 1, 1999; 54(7): 590 - 596. [Abstract] [Full Text]

				A. Jill Mackarel, D. C. Cottell, K. J. Russell, M. X. FitzGerald, and C. M. O'Connor Migration of Neutrophils across Human Pulmonary Endothelial Cells Is Not Blocked by Matrix Metalloproteinase or Serine Protease Inhibitors Am. J. Respir. Cell Mol. Biol., June 1, 1999; 20(6): 1209 - 1219. [Abstract] [Full Text]

				T. Betsuyaku, J. Michael Shipley, Z. Liu, and R. M. Senior Neutrophil Emigration in the Lungs, Peritoneum, and Skin Does Not Require Gelatinase B Am. J. Respir. Cell Mol. Biol., June 1, 1999; 20(6): 1303 - 1309. [Abstract] [Full Text]

				M. BOSSE, J. CHAKIR, M. ROUABHIA, L.-P. BOULET, M. AUDETTE, and M. LAVIOLETTE Serum Matrix Metalloproteinase-9:Tissue Inhibitor of Metalloproteinase-1 Ratio Correlates with Steroid Responsiveness in Moderate to Severe Asthma Am. J. Respir. Crit. Care Med., February 1, 1999; 159(2): 596 - 602. [Abstract] [Full Text]

				C. Trocme, P. Gaudin, S. Berthier, C. Barro, P. Zaoui, and F. Morel Human B Lymphocytes Synthesize the 92-kDa Gelatinase, Matrix Metalloproteinase-9 J. Biol. Chem., August 7, 1998; 273(32): 20677 - 20684. [Abstract] [Full Text] [PDF]

				R. Mohan, S. K. Chintala, J. C. Jung, W. V. L. Villar, F. McCabe, L. A. Russo, Y. Lee, B. E. McCarthy, K. R. Wollenberg, J. V. Jester, et al. Matrix Metalloproteinase Gelatinase B (MMP-9) Coordinates and Effects Epithelial Regeneration J. Biol. Chem., January 11, 2002; 277(3): 2065 - 2072. [Abstract] [Full Text] [PDF]