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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:e1.)
© 2001 American Heart Association, Inc.

Vascular Biology

Chlamydia pneumoniae Proteins Induce Secretion of the 92-kDa Gelatinase by Human Monocyte– Derived Macrophages

Pirjo Vehmaan-Kreula; Mirja Puolakkainen; Matti Sarvas; Howard G. Welgus; Petri T. Kovanen

From the Wihuri Research Institute (P.V.-K., P.T.K.); the Haartman Institute (M.P.), Department of Virology, University of Helsinki; and the National Public Health Institute (M.S.), Department of Vaccines, Helsinki, Finland; and Parke-Davis Pharmaceuticals Research (H.G.W.), Ann Arbor, Mich.

Correspondence to Petri T. Kovanen, MD, PhD, Wihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, Finland. E-mail Petri.Kovanen{at}wri.fi

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.

Key Words: humans • monocytes • macrophages • cellular activation • inflammatory mediators

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