Effects of chemically modified heparin on Chlamydia trachomatis serovar L2 infection of eukaryotic cells in culture.
The mechanism and inhibitors of Chlamydia trachomatis serovar L2 infection of eukaryotic host cells were studied using a tissue culture model infection system. Potent inhibition of infectivity was observed when elementary bodies (EBs) were exposed to heparin or when HeLa 229 cells were treated with heparinase. No significant inhibition was seen the other way around. The same potent inhibition was observed when EBs were exposed to chemically 2-O-desulfated heparin (2-ODS heparin), which is composed of repeating disaccharide units of IdoA-GlcNS(6S), but not when exposed to chemically 6-ODS heparin or completely desulfated and N-resulfated heparin, which is composed of repeating disaccharide units of IdoA(2S)-GlcNS or IdoA-GlcNS, respectively. The inhibitory effects of 2-ODS heparin could be seen only with oligosaccharides longer than dodecasaccharides. The mutant Chinese hamster ovary (CHO) cell line 677, which is deficient in the biosynthesis of heparan sulfate, was less sensitive to C. trachomatis infection than were wild-type CHO cells. F-17 cells, deficient in 2-O-sulfation of heparan sulfate, had the same sensitivity to infection as wild-type CHO cells did. These data suggest that infection of host cells by EBS results from the specific binding of ligand molecules with affinity for heparin on the EB surface to heparan sulfate proteoglycans on the host cell surface. This binding may depend on host cell heparan sulfate chains that are 6-O-sulfated and longer than dodecasaccharides. The 2-ODS heparin oligosaccharides may be a potential agent for the prevention of C. trachomatis infection.
Yabushita
Hiromitsu
H
Department of Obstetrics and Gynecology, Research Center for Infectious Disease, School of Medicine, Aichi Medical University, 21 Karimata, Nagakute-cho, Japan.
Noguchi
Yasuyuki
Y
Habuchi
Hiroko
H
Ashikari
Satoko
S
Nakabe
Ken
K
Fujita
Masaru
M
Noguchi
Masayoshi
M
Esko
Jeffrey D
JD
Kimata
Koji
K
D000818:Animals; D016466:CHO Cells; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000472:pathogenicity; D006224:Cricetinae; D006367:HeLa Cells; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology; D006493:Heparin / Q000494:pharmacology*; D019763:Heparin Lyase / Q000494:pharmacology; D006801:Humans
D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D019763:Heparin Lyase