Previous Article | Next Article 
Infection and Immunity, June 1999, p. 2909-2915, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Chlamydia pneumoniae Infection of Human
Endothelial Cells Induces Proliferation of Smooth Muscle Cells via an
Endothelial Cell-Derived Soluble Factor(s)
Brian K.
Coombes,1,* and
James B.
Mahony1,2
Regional Virology and Chlamydiology
Laboratory1 and Department of Pathology
and Molecular Medicine,2 McMaster
University, Hamilton, Ontario, Canada L8N 4A6
Received 22 February 1999/Returned for modification 17 March
1999/Accepted 26 March 1999
An association of Chlamydia pneumoniae with
atherosclerosis and coronary heart disease has been determined
epidemiologically and by the detection of C. pneumoniae
organisms in atherosclerotic lesions in both humans and animal models
of atherosclerosis. Previously, it has been shown that C. pneumoniae is capable of replicating in cell types found within
atheromatous lesions, viz., endothelial cells, smooth muscle cells
(SMC), and macrophages, yet the role of C. pneumoniae in
the pathogenesis of atherosclerosis has not been determined. Since
intimal thickening is a hallmark of atherosclerosis, we investigated
whether C. pneumoniae infection of human umbilical vein
endothelial cells (HUVEC) could induce the expression of a soluble
factor(s) with mitogenic potential for SMC by using [3H]thymidine incorporation and direct cell counting.
Conditioned medium harvested from HUVEC infected with C. pneumoniae stimulated SMC replication in a time- and
dose-dependent fashion. Infection studies using various multiplicities
of infection (MOIs) ranging from 0.001 to 1 demonstrated a
dose-dependent production of the soluble factor(s). At an MOI of 1, SMC
stimulation indices were 8.4 (P < 0.01) and 12.2 (P < 0.01) for conditioned media harvested at 24 and
48 h, respectively. To determine whether viable C. pneumoniae was required for production of the soluble factor(s),
HUVEC were infected with heat-inactivated C. pneumoniae or
with viable organisms in the presence of chloramphenicol. Both
treatments produced stimulation indices similar to those for live
C. pneumoniae in the absence of chloramphenicol
(P > 0.05), indicating that the factor(s) was produced by HUVEC and not by C. pneumoniae and that signal
transduction events following chlamydia endocytosis may be important in
the production of a soluble factor(s). The ability of C. pneumoniae to elicit an endothelial cell-derived soluble
factor(s) that stimulates SMC proliferation may be important in the
pathogenesis of atherosclerosis.
*
Corresponding author. Mailing address: Regional
Virology and Chlamydiology Laboratory, St. Joseph's Hospital, 50 Charlton Ave. E., Hamilton, Ontario, Canada L8N 4A6. Phone:
905-521-6021. Fax: 905-521-6083. E-mail:
coombebk{at}fhs.mcmaster.ca.
Infection and Immunity, June 1999, p. 2909-2915, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Epstein, S. E., Zhu, J., Najafi, A. H., Burnett, M. S.
(2009). Insights Into the Role of Infection in Atherogenesis and in Plaque Rupture. Circulation
119: 3133-3141
[Full Text]
-
Corcionivoschi, N., Clyne, M., Lyons, A., Elmi, A., Gundogdu, O., Wren, B. W., Dorrell, N., Karlyshev, A. V., Bourke, B.
(2009). Campylobacter jejuni Cocultured with Epithelial Cells Reduces Surface Capsular Polysaccharide Expression. Infect. Immun.
77: 1959-1967
[Abstract]
[Full Text]
-
Chen, S., Sorrentino, R., Shimada, K., Bulut, Y., Doherty, T. M., Crother, T. R., Arditi, M.
(2008). Chlamydia pneumoniae-Induced Foam Cell Formation Requires MyD88-Dependent and -Independent Signaling and Is Reciprocally Modulated by Liver X Receptor Activation. J. Immunol.
181: 7186-7193
[Abstract]
[Full Text]
-
Balsara, Z. R., Misaghi, S., Lafave, J. N., Starnbach, M. N.
(2006). Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1.. Infect. Immun.
74: 5602-5608
[Abstract]
[Full Text]
-
Jandu, N., Ceponis, P. J. M., Kato, S., Riff, J. D., McKay, D. M., Sherman, P. M.
(2006). Conditioned Medium from Enterohemorrhagic Escherichia coli-Infected T84 Cells Inhibits Signal Transducer and Activator of Transcription 1 Activation by Gamma Interferon. Infect. Immun.
74: 1809-1818
[Abstract]
[Full Text]
-
Hauer, A.D., de Vos, P., Peterse, N., ten Cate, H., van Berkel, Th.J.C., Stassen, F.R.M., Kuiper, J.
(2006). Delivery of Chlamydia pneumoniae to the vessel wall aggravates atherosclerosis in LDLr-/- mice. Cardiovasc Res
69: 280-288
[Abstract]
[Full Text]
-
Rupp, J., Hellwig-Burgel, T., Wobbe, V., Seitzer, U., Brandt, E., Maass, M.
(2005). Chlamydia pneumoniae infection promotes a proliferative phenotype in the vasculature through Egr-1 activation in vitro and in vivo. Proc. Natl. Acad. Sci. USA
102: 3447-3452
[Abstract]
[Full Text]
-
Rodel, J., Prochnau, D., Prager, K., Baumert, J., Schmidt, K.-H., Straube, E.
(2004). Chlamydia pneumoniae Decreases Smooth Muscle Cell Proliferation through Induction of Prostaglandin E2 Synthesis. Infect. Immun.
72: 4900-4904
[Abstract]
[Full Text]
-
Ludewig, B., Krebs, P., Scandella, E.
(2004). Immunopathogenesis of atherosclerosis. J. Leukoc. Biol.
76: 300-306
[Abstract]
[Full Text]
-
Rutger Persson, G., Ohlsson, O., Pettersson, T., Renvert, S.
(2003). Chronic periodontitis, a significant relationship with acute myocardial infarction. Eur Heart J
24: 2108-2115
[Abstract]
[Full Text]
-
Selzman, C. H., Netea, M. G., Zimmerman, M. A., Weinberg, A., Reznikov, L. L., Grover, F. L., Dinarello, C. A.
(2003). Atherogenic effects of Chlamydia pneumoniae: refuting the innocent bystander hypothesis. J. Thorac. Cardiovasc. Surg.
126: 688-693
[Abstract]
[Full Text]
-
Kalayoglu, M. V., Libby, P., Byrne, G. I.
(2002). Chlamydia pneumoniae as an Emerging Risk Factor in Cardiovascular Disease. JAMA
288: 2724-2731
[Abstract]
[Full Text]
-
Vainas, T., Kurvers, H. A.J.M., Mess, W. H., Graaf, R. d., Ezzahiri, R., Tordoir, J. H.M., Schurink, G.-W. H., Bruggeman, C. A., Kitslaar, P. J.E.H.M.
(2002). Chlamydia pneumoniae Serology Is Associated With Thrombosis-Related but Not With Plaque-Related Microembolization During Carotid Endarterectomy. Stroke
33: 1249-1254
[Abstract]
[Full Text]
-
Theegarten, D., Anhenn, O., Aretz, S., Maass, M., Mogilevski, G.
(2002). Detection of Chlamydia pneumoniae in unexplained pulmonary hypertension. Eur Respir J
19: 192-194
[Abstract]
[Full Text]
-
Coombes, B. K., Mahony, J. B.
(2001). cDNA Array Analysis of Altered Gene Expression in Human Endothelial Cells in Response to Chlamydia pneumoniae Infection. Infect. Immun.
69: 1420-1427
[Abstract]
[Full Text]
-
Pantoja, L. G., Miller, R. D., Ramirez, J. A., Molestina, R. E., Summersgill, J. T.
(2000). Inhibition of Chlamydia pneumoniae Replication in Human Aortic Smooth Muscle Cells by Gamma Interferon-Induced Indoleamine 2,3-Dioxygenase Activity. Infect. Immun.
68: 6478-6481
[Abstract]
[Full Text]
-
Fong, I. W.
(2000). Emerging relations between infectious diseases and coronary artery disease and atherosclerosis. CMAJ
163: 49-56
[Abstract]
[Full Text]
-
Rodel, J., Woytas, M., Groh, A., Schmidt, K.-H., Hartmann, M., Lehmann, M., Straube, E.
(2000). Production of Basic Fibroblast Growth Factor and Interleukin 6 by Human Smooth Muscle Cells following Infection with Chlamydia pneumoniae. Infect. Immun.
68: 3635-3641
[Abstract]
[Full Text]
-
Sasu, S., LaVerda, D., Qureshi, N., Golenbock, D. T., Beasley, D.
(2001). Chlamydia pneumoniae and Chlamydial Heat Shock Protein 60 Stimulate Proliferation of Human Vascular Smooth Muscle Cells via Toll-Like Receptor 4 and p44/p42 Mitogen-Activated Protein Kinase Activation. Circ. Res.
89: 244-250
[Abstract]
[Full Text]