MEMBRANE-COMPONENTS OF TREPONEMA-DENTICOLA TRIGGER PROTEINASE RELEASEFROM HUMAN POLYMORPHONUCLEAR LEUKOCYTES

Tissue destruction during periodontitis is believed to be primarily br ought about by leukocyte proteinases. We postulate that oral spirochet es cause discharge of polymorphonuclear leukocyte (PMN) lysosomal enzy mes. Effects of Treponema denticola 53-kDa outer membrane protein, lip opolysaccharide (LPS), and peptidoglycan on degranulation of matrix me talloproteinases (MMP)-8 (collagenase) and -9 (gelatinase), cathepsin G, and elastase by human peripheral blood PMNs were studied by specifi c enzyme assays and Western blot analysis. T. denticola 53-kDa outer m embrane protein was found to be a particularly efficient inducer of MM P-8 release. The induction was comparable with that of phorbol myrista te acetate, a known inducer of PMN specific granule discharge. All of the treponemal substances, most notably the 53-kDa protein and LPS, in duced release of MMP-9, a component of C-type granules. Both collagena se and gelatinase released from PMNs were mostly in active forms. Rele ase of cathepsin G and elastase was also observed with the 53-kDa prot ein treatment. The other T. denticola substances did not induce releas e of these serine proteinases. Lactate dehydrogenase was not released from PMNs by the treatments, indicating that the degranulation was spe cific and not caused by toxic effects of the substances. This was conf irmed by transmission electron microscopy of PMNs treated with the 53- kDa protein that showed rapid vacuole formation and cell shape changes but no disintegration of the cells. Thus, T. denticola may participat e in the PMN-dependent extracellular matrix degradation during the cou rse of periodontal inflammation by triggering the secretion and activa tion of matrix metalloproteinases.