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Infection and Immunity, January 2001, p. 456-462, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.456-462.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Borrelia Spirochetes Upregulate Release and Activation of Matrix Metalloproteinase Gelatinase B (MMP-9) and Collagenase 1 (MMP-1) in Human Cells

Joseph A. Gebbia,1 James L. Coleman,2 and Jorge L Benach1,3,*

Department of Pathology,1 State of New York Department of Health,2 and Department of Molecular Genetics and Microbiology, Center for Infectious Diseases,3 State University of New York at Stony Brook, Stony Brook, New York 11794

Received 28 July 2000/Returned for modification 8 September 2000/Accepted 6 October 2000

Borrelia burgdorferi, the spirochetal agent of Lyme disease, stimulated human peripheral blood monocytes to release pro-matrix metalloproteinase-9 (gelatinase B; pro-MMP-9) and active matrix metalloproteinase-1 (collagenase-1; MMP-1). Human neutrophils also released pro-MMP-9 and a 130-kDa protein with gelatinolytic activity in response to live B. burgdorferi. In addition, U937 cells and human keratinocyte cells were also stimulated to release pro-MMP-9 under the same conditions. However, human umbilical vein endothelial cells (HUVECs) released pro-MMP-9 and pro-MMP-2 in a constitutive manner and were not influenced by live spirochetes. MMPs produced by human monocytes also enhanced the penetration of B. burgdorferi through extracellular matrix component barriers in vitro. Plasmin stabilized on the surface of the Lyme disease spirochete was shown to activate pro-MMP-9 to its active form. This active form was also observed in the plasma of mice infected with a relapsing fever borrelia. These results suggest that borreliae can upregulate MMPs and possibly mediate an activation cascade initiated by plasmin bound to the microbial surface. MMPs may play a role in dissemination of the Lyme disease spirochete and in the pathogenesis of Borrelia infection.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, SUNY at Stony Brook, Stony Brook, NY 11794. Phone: (631) 632-4225. Fax: (631) 632-4294. E-mail: jbenach{at}notes.cc.sunysb.edu.

Infection and Immunity, January 2001, p. 456-462, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.456-462.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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