Phagocytosis and Intracellular Killing

After the MIC has been determined, it is necessary to decide whether the results suggest whether the organisms are susceptible to the tested antimicrobial in vivo. This decision requires an understanding of the PK of the dmg (see Chapter 2 for discussion) and other factors. For example, in vitro assessments of activity may underestimate the in vivo activity because of a post-antibiotic effect and post-antibiotic leukocyte enhancement. The post-antibiotic ejfect (PAE) refers to a persistent antibacterial effect at subinhibitory concentrations, whereas the term post-antibiotic leukocyte enhancement term (PALE) refers to the increased susceptibility to phagocytosis and intracellular killing demonstrated by bacteria following exposure to an antimicrobial agent. ... 

There has been some concern about the possible effects of factor VIII formulations on the immune system. In vitro experiments with coagulation factor concentrates have shown immunosuppressive effects (16,17), such as the impairment of Fc receptor-mediated phagocytosis and intracellular bacterial killing (18). Inhibition of IL-2 production, an impaired MLR, and impairment of PHA transformation have been demonstrated (19). A fall in the number of T4 lymphocytes has also been found. Whether these findings reflect functional impairment of the immune system is still unclear. 

A preparation of . purpurea expressed sap increased the in vitro phagocytosis of Candida albicans by granulocytes and monocytes from healthy donors by 30-45%. The chemotactic migration of granulocytes in the Boy den Chamber was increased by 45%. There was no effect in either direction on intracellular killing of... 

Pretreatment with Tinospora cordifolia was found to significantly reduce the mortality of Escherichia co//-induced peritonitis in a mouse model (16.7% in Tinospora cordifolia treated mice as compared to 100% in control mice) [20]. Bacterial clearance studies (up to 4 h after injection of Escherichia coli) revealed that in the Tinospora cordifolia treated mice, although the bacterial count increased initially, it dropped after the second hour. The phagocytic and intracellular bactericidal capacity of polymorphs of Tinospora cordifolia-treated mice were significantly increased (phagocytosis 56.7 5.7%, intracellular killing capacity (ICK) 52.4 5.5%) as compared to control (phagocytosis 34.3 3.4%, ICK 30.5 6.1%, p< 0.001) [21]. 

It is misleading to consider that ROS are always deleterious, and that to prevent release or action of ail ROS will be of therapeutic value. One could reason that some ROS are released without control or purpose, as by-products of the normal metabolism of eicosanoids, or during oxidative phosphorylation in the mitochondria. However, during normal function, inflammatory ceUs appropriately release ROS both intracellularly into vacuoles and extracellularly in order to kill foreign organisms in host defence. Also, nitric oxide is a radical species whose principal role in the lung appears to be the control of pulmonary vascular tone and platelet function. Nevertheless, there are clear examples where fhistrated phagocytosis could explain an excessive release of ROS in... 

Experimental data suggest that upregulation of complement receptor (CR3) and CR3-mediated phagocytosis are mechanisms by which TNFa and IFNy stimulate nonphagocytic, nonbactericidal macrophage precursors to kill intracellular bacterial pathogens. ... 

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