Elevated adenosine cyclic 3',5'-monophosphate levels in human macrophages following their interaction with Salmonella typhimurium.

The mechanisms by which salmonella species establish themselves as facultative intracellular parasites are incompletely understood. , strain TML, has been shown to elevate adenosine cyclic 3′, 5′-monophosphate (cAMP) levels in rabbit ileum. Since pharmacological elevation of cAMP content is inhibitory to many phagocytic cell functions, we sought to determine if strain TML would induce elevation of cAMP in human monocyte-derived macrophages and thereby establish itself as a facultative intracellular organism. strain SL does not affect cAMP levels in the rabbit ileum and served as a control organism. Both strains were used to infect human macrophages and the cAMP content of the macrophages measured by radioimmunoassay. Macrophages infected with strain TML had significantly (<0.025) higher levels of cAMP at 4, 10 and 24 hr after infection, 19.3±2.5, 17.6±2.4 and 15.4±1.7 pmol per mg protein respectively, than either uninfected macrophages or macrophages infected with strain SL. The cAMP content of SL-infected macrophages did not differ from that of uninfected macrophages. Quantification of intracellular bacteria over 48 hr revealed that strains TML and SL were ingested and killed to the same degree. Furthermore, the 7–10 day old human macrophages used in this study eliminated over 99% of the ingested organisms within 24 hr. Thus, TML was capable of inducing significant and sustained elevation of cAMP within human macrophages but was not capable of survival within this cell under the conditions of this study.