Phagocytes, bactericidal

While it may be desirable to limit the excess, chronic and inappropriate generation of phagocyte-derived ROMs, it is necessary to achieve this without simultaneously compromising their vital bactericidal function. The orally effective iron chelator 2,3-dihydroxybenzoate has been shown to decrease PMN ROM generation without a corresponding loss of bactericidal activity to phagocytosed Staphylococctis aureus (Boxer et al., 1978). 

In vivo studies showed that in vitro proliferation of lymphocytes isolated from marijuana smokers is suppressed, especially with heavy marijuana smoking, and that the relative proportion of lymphocyte subpopulations was also altered. Concentrations of serum IgG are decreased and IgE concentrations are increased in marijuana smokers. Furthermore, phagocytic and bactericidal activity of alveolar macrophages from heavy marijuana smokers are decreased. These effects translate into reduced host resistance following administration of cannabinoids, including THC, in both humans and animals (Table 30.2). Increased susceptibility has been demonstrated to opportunistic microbes including HIV, Herpes simplex virus, Friend leukemia virus Listeria, Treponema pallidum, and Legionella. 

Mechanisms by which ozone might interfere with bactericidal function include an alteration in cell-membrane function that produces a loss in phagocytic ability and is perhaps mediated by lipid peroxides and a decrease in the ability of veolar macrophages to kill phagocytized bacteria. Leukocytes in general appear to have a multiplicity of mechanisms for destroying ingested bacteria. 

Clofazimine is a weakly bactericidal dye that has some activity against M. leprae. Its precise mechanism of action is unknown but may involve mycobacterial DNA binding. Its oral absorption is quite variable, with 9 to 70% of the drug eliminated in the feces. Clofazimine achieves significant concentrations in tissues, including the phagocytic cells it has a plasma half-life of 70 days. It is primarily excreted in bile, with less than 1% excretion in urine. 

Rifampin binds to the 3 subunit of bacterial DNA-dependent RNA polymerase and thereby inhibits RNA synthesis. Resistance results from any one of several possible point mutations in rpoB, the gene for the 3 subunit of RNA polymerase. These mutations result in reduced binding of rifampin to RNA polymerase. Human RNA polymerase does not bind rifampin and is not inhibited by it. Rifampin is bactericidal for mycobacteria. It readily penetrates most tissues and penetrates into phagocytic cells. It can kill organisms that are poorly accessible to many other drugs, such as intracellular organisms and those sequestered in abscesses and lung cavities. 

Further, acidic peptide fractions from Atlantic cod hydrolysate have shown strong immunostimulatory effects, and treatment of these peptides has stimulated the oxidative burst of Atlantic salmon leucocytes (Gildberg et al., 1996). Basically, immunomodulators that enhance the production of oxygen metabolites in macrophages that are responsible for these oxygen metabolites determine the oxidative burst. Oxidative burst reactions are of major importance for the bactericidal power of phagocytes. 

In vitro, isoniazid inhibits most tubercle bacilli in a concentration of 0.2 g/mL or less and is bactericidal for actively growing tubercle bacilli. Isoniazid is less effective against atypical mycobacterial species. Isoniazid is able to penetrate into phagocytic cells and thus is active against both extracellular and intracellular organisms. 

Uropathogenic E. coli cause 90% of the urinary tract infections. The bacteria colonize from the feces or perineal region and ascend the urinary tract to the bladder. With the aid of specific adhesins (pyelonephritis-associated pili) they are able to colonize the bladder. Another factor involved in the pathogenicity of the uropathogenic strains of E. coli is their resistance to complement-dependent bactericidal effect of serum. This phenomenon is associated with the presence of a capsule, which decrease the ability of antibodies and/or complement to bind to the bacterial surface, which in turn prevents the phagocytes from recognizing and engulfing the bacterial cells. 

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