PMID- 11404367
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20061115
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 69
IP  - 6
DP  - 2001 Jun
TI  - Gelatinase B functions as regulator and effector in leukocyte biology.
PG  - 851-9
AB  - Matrix metalloproteinases (MMPs) form a family of enzymes with major actions in 
      the remodeling of extracellular matrix (ECM) components. Gelatinase B (MMP-9) is 
      the most complex family member in terms of domain structure and regulation of its 
      activity. Gelatinase B activity is under strict control at various levels: 
      transcription of the gene by cytokines and cellular interactions; activation of 
      the pro-enzyme by a cascade of enzymes comprising serine proteases and other 
      MMPs; and regulation by specific tissue inhibitors of MMPs (TIMPs) or by 
      unspecific inhibitors, such as alpha2-macroglobulin. Thus, remodeling ECM is the 
      result of the local protease load, i.e., the net balance between enzymes and 
      inhibitors. Glycosylation has a limited effect on the net activity of gelatinase 
      B, and in contrast to the all-or-none effect of enzyme activation or inhibition, 
      it results in a higher-level, fine-tuning effect on the ECM catalysis by 
      proteases in mammalian species. Fast degranulation of considerable amounts of 
      intracellularly stored gelatinase B from neutrophils, induced by various types of 
      chemotactic factors, is another level of control of activity. Neutrophils are 
      first-line defense leukocytes and do not produce gelatinase A or TIMP. Thus, 
      neutrophils contrast sharply with mononuclear leukocytes, which produce 
      gelatinase A constitutively, synthesize gelatinase B de novo after adequate 
      triggering, and overproduce TIMP-1. Gelatinase B is also endowed with functions 
      other than cleaving the ECM. It has been shown to generate autoimmune 
      neo-epitopes and to activate pro-IL-1beta into active IL-1beta. Gelatinase B 
      ablation in the mouse leads to altered bone remodeling and subfertility, results 
      in resistance to several induced inflammatory or autoimmune pathologies, and 
      indicates that the enzyme plays a crucial role in development and angiogenesis. 
      The major human neutrophil chemoattractant, IL-8, stimulates fast degranulation 
      of gelatinase B from neutrophils. Gelatinase B is also found to function as a 
      regulator of neutrophil biology and to truncate IL-8 at the amino terminus into a 
      tenfold more potent chemokine, resulting in an important positive feedback loop 
      for neutrophil activation and chemotaxis. The CXC chemokines GRO-alpha, CTAP-III, 
      and PF-4 are degraded by gelatinase B, whereas the CC chemokines MCP-2 and RANTES 
      are not cleaved.
FAU - Opdenakker, G
AU  - Opdenakker G
AD  - Laboratory of Molecular Immunology, Rega Institute, University of Leuven, Leuven, 
      Belgium. ghislain.opdenakker@rega.kuleuven.ac.be
FAU - Van den Steen, P E
AU  - Van den Steen PE
FAU - Dubois, B
AU  - Dubois B
FAU - Nelissen, I
AU  - Nelissen I
FAU - Van Coillie, E
AU  - Van Coillie E
FAU - Masure, S
AU  - Masure S
FAU - Proost, P
AU  - Proost P
FAU - Van Damme, J
AU  - Van Damme J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Autoimmune Diseases/enzymology
MH  - Chemokines/physiology
MH  - Chromosomes, Human, Pair 20/genetics
MH  - Cytokines/physiology
MH  - Enzyme Activation
MH  - Enzyme Induction
MH  - Extracellular Matrix/enzymology
MH  - Humans
MH  - Leukocytes/cytology/*enzymology
MH  - Leukocytes, Mononuclear/enzymology
MH  - Macromolecular Substances
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/chemistry/deficiency/genetics/immunology/*physiology
MH  - Neoplasms/enzymology
MH  - Neutrophils/cytology/enzymology
MH  - Organ Specificity
MH  - Phenotype
MH  - Protein Processing, Post-Translational
MH  - Protein Structure, Tertiary
MH  - Tissue Inhibitor of Metalloproteinase-1/metabolism
RF  - 73
EDAT- 2001/06/19 10:00
MHDA- 2001/08/03 10:01
CRDT- 2001/06/19 10:00
PHST- 2001/06/19 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/06/19 10:00 [entrez]
PST - ppublish
SO  - J Leukoc Biol. 2001 Jun;69(6):851-9.