Showing papers by "Myron S. Cohen published in 1991"

Phagocyte-derived free radicals stimulated by ingestion of iron-rich Staphylococcus aureus: a spin-trapping study.

Abstract: Phagocytic cells generate superoxide (O2-) and hydrogen peroxide (H2O2), creating the substrates for hydroxyl radical (HO.) in the presence of redox active metals. Previously it was shown that HO. is not a physiologic product of human neutrophils or monocytes but can be generated in the presence of high concentrations of iron. This study was undertaken to determine whether bacterial iron could be used for the generation of HO. The growth of Staphylococcus aureus under iron-rich conditions increased bacterial iron concentration and phagocytosis of iron-rich bacteria allowed neutrophils to accumulate threefold more iron than ingestion of iron-starved organisms. Neither neutrophils nor monocytes ingesting iron-rich S. aureus generated iron-catalyzed HO. at levels detectable by spin-trapping techniques. No differences in the killing of iron-rich organisms by neutrophils was noted. The results suggest that HO. does not play a role in the killing of S. aureus by human neutrophils, regardless of their ability to deliver iron to the cell.

Application of spin trapping to human phagocytic cells: insight into conditions for formation and limitation of hydroxyl radical.

Abstract: In recent years spin trapping techniques have been used extensively to better understand the free radical biology of phagocytic cells. These results demonstrate that spin trapping is of adequate sensitivity to detect superoxide and/or hydroxyl radical generated by these cells, and that spin trapping is capable of measuring phagosomal radicals as well. However. neither neutrophils. monocytes. nor monocyte derived macro-phages generate hydroxyl radical in the absence of exogenous iron. Furthermore. neutrophil lactoferrin and myeloperoxidase limit the magnitude (and in the case of lactoferrin the duration) of hydroxyl radical formed by neutrophils in an iron catalyzed system. Since monocytic phagocytes posxss no lactoferrin, and limited myeloperoxidase, hydroxyl radical may play an important role in the inflammatory behavior of mononuclear phagocytes.

Phagocytes in health and disease

Abstract: Phagocytic cells are critical for defense against infection, but also play a key role in inflammation. Phagocytic cells engage in obligatory events, including attachment to blood vessel walls, activated chemotaxis, phagocytosis, and microbial killing. Attachment to blood vessels and extracellular membrane proteins depends on the activity of receptor proteins in the integrin class. In addition, phagocytic cells can recognize platelet-activating receptor and PADGEM protein presented by endothelial cells. Chemotaxis has been most widely studied to understand the transduction process. Activated chemotaxis depends on the interaction between GTP-binding proteins (leading to activation of phospholipase C or D), alteration of cellular calcium, and protein kinase-mediated phosphorylation of substrates. Phagocytosis depends on immunoglobulin and complement. It has been recognized that the phagocytosis of some opportunistic pathogens such as mycobacteria and legionella depend primarily on the third component of complement. Microbial killing depends on formation of reactive oxygen intermediates and microbial proteins. In addition, the formation of nitric oxide by phagocytes has recently received attention because of its importance in the killing of some fungi, protozoa, and tumor target cells. Phagocytes may act as hosts for some intracellular pathogens such as chlamydia and listeria. In addition, cytomegalovirus infects neutrophils and human immunodeficiency virus infects monocytic phagocytes. Difficulty in eliminating infection in these host cells will represent a key part of future antiviral therapy of these diseases.