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PubMed · 9507637

Mycobacterium tuberculosis and the complement system.

Abstract

Accumulated evidence to date confirms the importance of the C3-CR pathway in the phagocytosis of pathogenic mycobacteria. Detailed receptor-ligand studies for phagocytosis are creating the framework to test the hypothesis that the entry pathway for these bacteria influences the immediate host cell response and their intracellular fate. These types of study are particularly important for improving our understanding of the outcome of primary infection in humans, where the number of bacilli is presumed to be very low.

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BibTeXRIS

L S Schlesinger. 1998. Mycobacterium tuberculosis and the complement system.. https://doi.org/10.1016/s0966-842x(97)01203-1

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Complement is one of the integral buttresses of the inflammatory response. In addition to host defense activities, proinflammatory properties of several complement components are described. This overview elucidates the role of complement in inflammatory reactions in vitro and in vivo, focusing on the complement activation products, C5a, and the membrane attack complex, C5b-9. Using several approaches, the impact of these complement components in mechanisms relevant to neutrophil recruitment is emphasized. In addition, the participation of complement in endothelial superoxide generation and its essential requirement for full expression of lung injury is demonstrated, as are the involved intracellular signal transduction pathways. Understanding the mechanisms of complement-induced proinflammatory effects may provide a basis for future therapeutic blockade of complement and/or its activation products.

Complement Activation

Smokeless tobacco extracts activate complement in vitro: a potential pathogenic mechanism for initiating inflammation of the oral mucosa.

The use of smokeless tobacco has been linked to an increased incidence of inflammation of the buccal and gingival mucosa. However, the mechanisms by which smokeless tobacco initiates inflammation are not well understood. The complement cascade is a ubiquitous source of proinflammatory molecules and can be activated rapidly by a wide variety of agents. Therefore, the effect of smokeless tobacco on complement was investigated as a potential pathogenic mechanism for triggering inflammation of the oral mucosa. Aqueous extracts of loose leaf chewing tobacco (1S1), dry snuff (1S2), and moist snuff (1S3), added to normal human serum, depleted complement hemolytic activity in a dose-dependent manner. Experiments utilizing sera deficient in one specific complement component indicated that the smokeless tobacco-induced depletion of hemolytic activity was due largely to consumption of C3. Furthermore, assays designed to test the activity of the alternative pathway of complement clearly showed that all three extracts depleted the hemolytic activity of this pathway. Finally, all three smokeless tobacco extracts activated the alternative pathway since significantly elevated levels of the cleavage fragments iC3b and Bb were detected in extract-treated serum. High quantities of the classical pathway cleavage fragment C4d also were detected in serum treated with moist snuff (1S3). The results clearly demonstrate that smokeless tobacco extracts activate the alternative pathway and also suggest some measure of classical pathway activation. Activation of complement by smokeless tobacco may be a mechanism for initiating inflammation of the oral mucosa.

Complement Activation