The interactions of human polymorphonuclear neutrophils (PMNs) with virulent and avirulent strains of Salmonella typhi were examined. Ingestion of the S. typhi strains by PMNs was evaluated with three techniques: visual examination of PMN monolayers (phagocytic index); uptake of radiolabeled S. typhi by PMNs; and removal of S. typhi from the supernatant of suspensions of PMNs and bacteria. All three techniques indicated equivalent phagocytosis of the strains. Postphagocytic PMN oxidative metabolism was quantitated with measurements of oxygen consumption, protein iodination, and chemiluminescence. We found that although PMNs ingested equal numbers of virulent and avirulent S. typhi, those PMNs ingesting the virulent organisms exhibited a significantly smaller increase in postphagocytic oxidative metabolism than PMNs ingesting avirulent S. typhi. Despite this muted oxidative burst the virulent bacteria were killed as well as the avirulent strains. Virulent S. typhi either fail to stimulate receptors that trigger PMN oxidative metabolism or inhibit PMN oxidative metabolism. Our data support the former hypothesis.
Cyanobacteria
are an interesting source of biologically active natural products,
especially chemically diverse and potent protease inhibitors. On our
search for inhibitors of the trypanosomal cysteine protease rhodesain,
we identified the homodimeric cyclopentenedione (CPD) nostotrebin
6 (1) and new related monomeric, dimeric, and higher
oligomeric compounds as the active substances in the medium extract
of Nostoc sp. CBT1153. The oligomeric
compounds are composed of two core monomeric structures, a trisubstituted
CPD or a trisubstituted unsaturated δ-lactone. Nostotrebin 6
thus far has been the only known cyanobacterial CPD. It has been found
to be active in a broad variety of assays, indicating that it might
be a pan-assay interference compound (PAIN). Thus, we compared the
antibacterial and cytotoxic activities as well as the rhodesain inhibition
of selected compounds. Because a compound with a δ-lactone instead
of a CPD core structure was equally active as nostotrebin 6, the bioactivities
of these compounds seem to be based on the phenolic substructures
rather than the CPD moiety. While the dimers were roughly equally
potent, the monomer displayed slightly weaker activity, suggesting
that the compounds show unspecific activity depending upon the number
of free phenolic hydroxy groups per molecule.
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