title: Chlamydia pneumoniae proteins induce secretion of the 92-kDa gelatinase by human monocyte- derived macrophages.
abstract: Chlamydia pneumoniae, an intracellular Gram-negative respiratory bacterium, and macrophages are present in inflammatory tissue sites such as atherosclerotic lesions, where abnormal degradation of the extracellular matrix takes place. To evaluate the potential of C pneumoniae for participation in matrix destruction, we studied the effect of this bacterium on the production of 3 matrix-degrading metalloproteinases, 92-kDa gelatinase, interstitial collagenase-1, and stromelysin-1, and their natural inhibitor TIMP-1 (tissue inhibitor of metalloproteinases-1) by human monocyte-derived macrophages differentiated in vitro. Spontaneous production of collagenase and stromelysin by these cells was minimal and was not influenced by C pneumoniae. In contrast, the cells secreted substantial basal quantities of 92-kDa gelatinase, the secretion of which was stimulated (on average, 2.5-fold) by C pneumoniae. C pneumoniae regulated the expression of 92-kDa gelatinase by macrophages at the pretranslational level. Macrophages secreted only small quantities of TIMP-1. The chlamydial proteins Omp2, MOMP, and HSP60 were also found to participate in the induction of 92-kDa gelatinase by C pneumoniae. Denaturation of chlamydial proteins by boiling reduced 92-kDa gelatinase secretion only partially (by 35%), suggesting that the heat-stabile lipopolysaccharide molecules also stimulate secretion of the enzyme. The results show that production of 92-kDa gelatinase by human macrophages is selectively upregulated by C pneumoniae, which suggests that these bacteria, when present in a macrophage-containing inflammatory environment, actively participate in the destruction of the extracellular matrix.
authors.affiliation: Wihuri Research Institute, Department of Virology, University of Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Vehmaan-Kreula
authors.forename: M
authors.initials: M
authors.lastname: Puolakkainen
authors.forename: M
authors.initials: M
authors.lastname: Sarvas
authors.forename: H G
authors.initials: HG
authors.lastname: Welgus
authors.forename: P T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D001426:Bacterial Proteins / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000502:physiology; D016993:Chlamydophila pneumoniae / Q000145:classification / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D018093:Gelatinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006358:Hot Temperature; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000201:enzymology* / Q000382:microbiology*; D008565:Membrane Proteins / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000201:enzymology* / Q000382:microbiology*; D014176:Protein Biosynthesis; D012703:Serotyping; D013997:Time Factors
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D018834:Chaperonin 60; D008565:Membrane Proteins; C063931:Omp2 protein, bacteria; D018093:Gelatinases