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 hum an peripheral blood monocytes to release pro-matrix metalloproteinase-9 (ge latinase 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 w ith gelatinolytic activity in response to live B. burgdorferi. In addition, U937 cells and human keratinocyte cells were also stimulated to release pr o-MMP-9 under the same conditions. However, human umbilical vein endothelia l 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 monocyt es also enhanced the penetration of B. burgdorferi through extracellular ma trix 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 r elapsing fever borrelia. These results suggest that borreliae can upregulat e MMPs and possibly mediate an activation cascade initiated by plasmin boun d to the microbial surface. MMPs may play a role in dissemination of the Ly me disease spirochete and in the pathogenesis of Borrelia infection.