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Antibacterial resistance, macrophage influx, and activation induced by bacterial rRNA with
Abstract:
Intraperitoneally injected rRNA from Pseudomonas aeruginosa combined with dimethyldioctadecylammonium bromide (DDA) increased nonspecifically the resistance of mice against an intraperitoneal challenge with extracellular (P. aeruginosa, Escherichia coli) and intracellular (Listeria monocytogenes) bacteria. This study concerns the mechanism underlying the nonspecific resistance. RNA with DDA (RNA-DDA) induced a cell influx and activated peritoneal macrophages (M phi) as judged by the decreased 5'-nucleotidase and alkaline phosphodiesterase activities in M phi lysates, the enhanced O2- release, and the increased antitumor activity in comparison with unstimulated M phi. RNA without DDA did not enhance the resistance and did not influence the peritoneal cell numbers or M phi properties. DDA without RNA enhanced the resistance of mice only slightly; it induced a cell influx, yielding elicited M phi as judged by the decreased 5'-nucleotidase activity and increased alkaline phosphodiesterase activity, the slightly enhanced O2- release, and the absence of increased antitumor activity. Both RNA-DDA and DDA M phi showed an enhanced capacity to ingest and kill L. monocytogenes in vitro, DDA M phi being slightly less effective than RNA-DDA M phi with respect to killing. We conclude that the enhanced killing capacity of M phi for L. monocytogenes is characteristic of both elicited DDA M phi and activated RNA-DDA M phi. The relationship between nonspecific resistance, peritoneal cell numbers, and antibacterial M phi activity is discussed. In addition, it is shown that RNA and DDA retain their activity when they are injected apart, suggesting that they activate M phi by sequential action.
Insights
Ribonucleic acid (RNA) from Pseudomonas aeruginosa combined with dimethyldioctadecylammonium bromide (DDA) enhances nonspecific resistance in mice by activating peritoneal macrophages. This activation boosts the macrophages' ability to combat bacterial infections.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Nonspecific resistance in mice can be enhanced by intraperitoneal injection of Pseudomonas aeruginosa rRNA and dimethyldioctadecylammonium bromide (DDA).
- The underlying mechanisms of this enhanced resistance, particularly the role of peritoneal macrophages, require elucidation.
Purpose of the Study:
- To investigate the mechanism by which RNA-DDA confers nonspecific resistance against bacterial challenge.
- To characterize the activation state and functional properties of peritoneal macrophages following RNA-DDA or DDA administration.
Main Methods:
- Mice were injected intraperitoneally with Pseudomonas aeruginosa rRNA, DDA, or a combination (RNA-DDA).
- Peritoneal macrophages were isolated and assessed for cell influx, enzyme activities (5'-nucleotidase, alkaline phosphodiesterase), O2- release, and antitumor activity.
- In vitro assays evaluated the capacity of macrophages to ingest and kill Listeria monocytogenes.
Main Results:
- RNA-DDA significantly increased resistance against extracellular and intracellular bacteria, correlating with activated peritoneal macrophages.
- Activated macrophages exhibited decreased 5'-nucleotidase and alkaline phosphodiesterase activities, enhanced O2- release, and increased antitumor and antibacterial activity.
- DDA alone induced elicited macrophages with some, but not all, activation markers and provided only slight resistance enhancement.
Conclusions:
- The enhanced killing capacity of macrophages against Listeria monocytogenes is a key feature of both DDA-elicited and RNA-DDA-activated macrophages.
- RNA-DDA activates peritoneal macrophages, contributing to the observed nonspecific resistance.
- RNA and DDA may act sequentially to activate macrophages, retaining activity even when administered separately.