Control mechanisms governing the infectivity of Chlamydia trachomatis for hela cells: modulation by cyclic nucleotides, prostaglandins and calcium.
Chlamydia trachomatis causes common infections of the eyes and genital tract in man. The mechanism by which this obligate intracellular bacterium is taken into epithelial cells is unclear. The results described here support the concept that chlamydial infections of HeLa cells is under bidirectional cyclic nucleotide control, with guanosine 3':5'-cyclic monophosphate (cGMP) acting as a stimulator, and adenosine 3':5'-cyclic monophosphate (cAMP) as an inhibitor. Treatment of the HeLa cells with the divalent cation ionophore A23187, with carbamoylcholine, or with prostaglandins known to increase the concentration of endogenous cGMP, also increased host cell susceptibility to chlamydial infection. Cyclic GMP was only effective if added at or before chlamydial inoculation, suggesting that its main effect was on chlamydial uptake. The stimulatory effect of cGMP, but nt antagonism, by cAMP, was abolished if the cells were first treated with any of four different inhibitors of prostaglandin synthesis, suggesting a critical role for endogenous prostaglandin synthesis. Centrifugation of chlamydiae on to host cells was followed by a rapid increase in the mobility of Ca2+ across the cell membrane. The interrelationships of these observations and the possibility that chlamydiae and other intracellular pathogens might evoke alterations in host cell prostaglandin and cyclic nucleotide concentrations to aid their own uptake are discussed.
D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002692:Chlamydia trachomatis / Q000254:growth & development*; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D011453:Prostaglandins / Q000096:biosynthesis*
D011453:Prostaglandins; D003995:Dibutyryl Cyclic GMP; D000001:Calcimycin; D003994:Bucladesine; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium