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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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