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Title: Non-specific recognition by macrophages and mechanisms of macrophage activation
Author: Ogmundsdottir, H. M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1979
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This study deals with two related aspects of macrophage function, surface recognition and signal transmission across the plasma membrane. The introduction reviews the properties and functions of macrophages with particular reference to specific and non-specific recognition and activation as expressed by enhanced effector function. This review is set against the background of the structure and function of plasma membranes, biological recognition and mechanisms of cellular activation. The ability of macrophages to recognize a variety of foreign particles without the mediation of specific recognition molecules was investigated. In a binding assay performed at 4°C using non-opsonized bacteria, it was found that several types of Gram-positive and Gram-negative bacteria bound to normal mouse peritoneal macrophages. The binding could be inhibited by pre-incubating the macrophages at 4°C with various monosaccharides at a concentration of 10 aM. There was a very close correlation between the ability of a sugar to inhibit binding of a particular type of bacterium and the presence of that sugar in the bacterial cell wall. It was, therefore, postulated that the binding of non-opsonized bacteria by macrophages was based on the recognition of cell wall carbohydrates. The nature of the binding reaction was further studied using Corvnebacterium parvum. It was found that binding at 4°C depended on the presence of both Ca++- and MgtLions whilst binding at 20°C occurred to some degree when only Mg++-ions were present. The binding was not mediated by cell-bound antibody as shown by experiments using mild trypsin-treatment and specific antibody. Pro-treatment of the macrophages with trypain, process, /3-galactosidase and phospholipases A, C and D caused a marked reduction in binding whilst treatment with neuraminidase resulted in some increase in binding. Exposure of the macrophages to periodate also led to a decrease in binding of C. parvum, an effect largely reversed by subsequent treatment with borohydride. Recovery from the effects of enzyme treatment was rapid, but was inhibited by EDT& in the case of trypsin and β3-galactosidase. These results suggested that plasma membrane glycoproteins played an important part in the binding reaction which might involve a bridging action of divalent cations. The effect of neuraminidase was most easily explained by a reduction in cell surface negative charge. The enhancement of phosphatidyl inositol turnover was investigated as a possible mechanism of signal transmission initiating the intracellular effects of an activating agent following contact with the macrophage surface. The rate of phosphatidyl inositol turnover was assayed by measuring the uptake of tritiated Wo-iuositol into macrophage phosphatidyl inositol during one hour, It was shown that two macrophage activating agents, endotoxin and C. parvum caused an increase in phosphatidyl inositol turnover after 4 hours of incubation whilst exposure to three inert particles, Staphylococcus albus, latex and collol 1 carbon, had no such effect. All the particles tested were phagooytoses, and it was concluded that enhanced turnover of phosphatidyl inolitol was an ear1y event following exposure to activating agents that was not linked to the process of phagocytosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available