Article

Staphylococcal Superantigen-Like Protein 5 Inhibits Matrix Metalloproteinase 9 from Human Neutrophils

Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Shinagawa-ku, Tokyo, Japan.
Infection and immunity (Impact Factor: 3.73). 07/2010; 78(7):3298-305. DOI: 10.1128/IAI.00178-10
Source: PubMed

ABSTRACT

Staphylococcal superantigen-like proteins (SSLs) constitute a family of exoproteins exhibiting structural similarities to
superantigens and enterotoxins but no superantigenic activity. In this article, we present evidence that SSL5 specifically
binds to matrix metalloproteinase 9 (MMP-9) and inhibits its enzymatic activity. When human neutrophil cell lysate was applied
to recombinant His-tagged SSL5 conjugated to Sepharose, the bound fraction gave a major band of approximately 100 kDa in SDS-polyacrylamide
gel electrophoresis. This protein was identified as the proform of MMP-9 (proMMP-9) by peptide mass fingerprinting analysis.
The recombinant SSL5-Sepharose also bound to proMMP-9 secreted by interleukin 8 (IL-8)-stimulated neutrophils and HT1080 fibrosarcoma
cells. Surface plasmon resonance analysis revealed that recombinant SSL5 bound to proMMP-9 with rather high affinity (dissociation
constant [KD] = 1.9 nM). Recombinant SSL5 was found to effectively inhibit MMP-9-catalyzed hydrolysis of gelatin and a synthetic fluorogenic
peptide in a noncompetitive manner (Ki = 0.097 nM), as assessed by zymography and the fluorescence quenching method. Finally, the transmigration of neutrophils
across Matrigel basement membranes in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was suppressed by the presence of recombinant SSL5. We discuss possible roles
that SSL5 may play in immune evasion of staphylococci by inhibiting MMP and interfering with leukocyte trafficking.

Download full-text

Full-text

Available from: Teruaki Oku, Jun 20, 2014
  • Source
    • "The staphylococcal SSL5 binds PSGL1 in a glycan dependent manner at the surface of neutrophils, blocking its interaction with P-selectin expressed by endothelial cells and abrogating the early steps of neutrophil attachment (Bestebroer et al., 2007). In addition, SSL5 was shown to inactivate matrix metalloproteinase from human neutrophils, accounting for the limited capacity of neutrophils to transmigrate into infected tissues (Itoh et al., 2010). The extracellular adherence protein (Eap) recognizes endothelial ICAM1, preventing its interaction with β2-integrins at the surface of neutrophils and further inhibiting extravasation (Chavakis et al., 2002). "

    Full-text · Dataset · Feb 2016
  • Source
    • "2.6. MMP-9 activity assay MMP-9 activity was measured by the fluorescence method using a fluorescent peptide (Itoh et al., 2010). Pro-MMP-9 in tissue samples was activated by treatment with 0.75 mM p-aminophenylmercuric acetate (Sigma-Aldrich) at 37 °C for 1 h. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present study was to investigate effect of two different ages (6weeks [6W] vs. 6months [6M]) on blood-brain barrier (BBB) disruption in EAE and evaluate the expression and correlations of NADPH oxidase, MMP-9, ICAM-1, and VCAM-1 following increased age and EAE induction. Higher disease severity was observed in 6M-EAE than 6W-EAE. The four factors were significantly elevated and correlated in 6M-EAE. BBB permeability increased with statistically significant interaction between age and EAE effects. We suggest strong correlations between NADPH oxidase and the other factors play important roles in increased BBB disruption and EAE susceptibility in middle-aged mice.
    Preview · Article · Aug 2015 · Journal of neuroimmunology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Macrophages that infiltrate tumor tissues, or tumor-associated macrophages (TAMs), affect the malignant behaviors of tumor cells. In this study, we attempted to induce monocytes to differentiate into TAM-like cells producing matrix metalloproteinases (MMPs) by co-culture with tumor cells. When human monocytes were co-cultured for 3-7 days with tumor cell lines, monocytes differentiated to produce MMP-9, accompanied by morphological changes. The in vitro cell invasion of MKN1 human gastric carcinoma cells into Matrigel membranes was promoted in the presence of differentiated monocytes, and the enhancement of cell invasion by differentiated monocytes was correlated with their MMP-9 productivity. The addition of an RGD (Arg-Gly-Asp) peptide to the culture significantly inhibited monocyte differentiation. The MMP-9 production from monocytes was diminished by the depletion of fibronectin from the conditioned media with gelatin-Sepharose, and potentiated by culturing them in fibronectin-coated plates. These results suggest that cell adhesion to the extracellular matrix plays a crucial role in monocyte differentiation into TAM-like cells.
    No preview · Article · Nov 2011 · Cancer letters
Show more