title: Differential induction of gelatinase B (MMP-9) and gelatinase A (MMP-2) in T lymphocytes upon alpha(4)beta(1)-mediated adhesion to VCAM-1 and the CS-1 peptide of fibronectin.
abstract: Integrin alpha(4)beta(1) on the surface of T lymphocytes interacts with vascular cell adhesion molecule-1 (VCAM-1) and fibronectin during migration of lymphocytes from the blood to sites of inflammation. Migrating lymphocytes actively modify their environment through a number of mechanisms including proteolysis of the extracellular matrix by matrix metalloproteinases (MMP) synthesized by the cells. In this study, expression of MMP upon alpha(4)beta(1)-mediated adhesion of leukocytes to two major ligands, the IIICS-1 domain of fibronectin and VCAM-1, has been examined. Adhesion of T lymphoblastoid Jurkat cells to the CS-1 peptide induced expression of mRNA for two MMPs, gelatinase A (MMP-2) and gelatinase B (MMP-9). As evaluated by relative RT-PCR and Northern blot analyses, the level of mRNA was upregulated about 4- to 5-fold for both MMPs compared to control cells maintained in suspension. With time, both enzymes were detected in conditioned media and inside the cells, and their identities were verified by Western blotting and gelatin zymography. Adhesion of Jurkat cells to the second major alpha(4)beta(1) ligand, VCAM-1, upregulated mRNA for MMP-2 (3.5-fold) and failed to induce expression of mRNA for MMP-9. Accordingly, only MMP-2 protein was detected in conditioned media of cells adherent to VCAM-1. Occupancy of alpha(4)beta(1) on the surface of suspended cells with soluble CS-1 peptide or VCAM-1 did not upregulate synthesis and release of MMPs. A similar pattern of induction of MMPs after adhesion to CS-1 and VCAM-1 was observed in T lymphocytes isolated from human blood. These results demonstrate that adhesion of T lymphocytes through alpha(4)beta(1) to different ligands, which bind to similar or overlapping sites in the integrin, induces intracellular events leading to distinct patterns of MMPs biosynthesis.
authors.affiliation: Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute of the Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: V P
authors.initials: VP
authors.lastname: Yakubenko
authors.forename: R R
authors.initials: RR
authors.lastname: Lobb
authors.forename: E F
authors.initials: EF
authors.lastname: Plow
authors.forename: T P
authors.initials: TP
authors.lastname: Ugarova
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D004790:Enzyme Induction; D005353:Fibronectins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D019169:Jurkat Cells; D007700:Kinetics; D008024:Ligands; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D008024:Ligands; D009842:Oligopeptides; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; C094697:glutamyl-isoleucyl-leucyl-aspartyl-valine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9