Borrelia spirochetes upregulate release and activation of matrix metalloproteinase gelatinase B (MMP-9) and collagenase 1 (MMP-1) in human cells.
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.
Gebbia
J A
JA
Department of Pathology, Center for Infectious Diseases, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
Coleman
J L
JL
Benach
J L
JL
D000818:Animals; D015748:Borrelia burgdorferi Group / Q000502:physiology*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000201:enzymology; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D005341:Fibrinolysin / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology; D008193:Lyme Disease / Q000201:enzymology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009000:Monocytes / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology; D015854:Up-Regulation
D004792:Enzyme Precursors; D005341:Fibrinolysin; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1