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Chapter 19 : Macrophage Classical Activation
- Type: Chapter
- Authors: Donald C. Vinh, Steven M. Holland
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Source: Phagocyte-Pathogen Interactions , pp 301-323
Publication Date :
January 2009
- DOI 10.1128/9781555816650.ch19
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Abstract:
This chapter focuses on the critical steps of classical macrophage activation that have been emphasized by rare human diseases in which key components such as macrophages, are naturally deficient. In conjunction with other cells, macrophages will form granulomas. Numerous molecules are definitely or putatively involved in this process, and a few have been identified by natural mutations. The author reviews these through an arbitrary and artificial division of the proinflammatory response into premacrophage, intramacrophage, and post-macrophage phases. The activated TAK-1 activates the IκB kinase (IKK) complex; this complex is composed of two catalytic subunits, IKK αand IKK β, and the regulatory subunit IKKγ. Peripheral blood monocytes and primary macrophage cultures from patients with classical Wiskott-Aldrich syndrome (WAS) also demonstrate impaired FcγR-mediated phagocytosis due to defective phagocytic cup formation. Previous explanations for the selective infection susceptibility in chronic granulomatous disease (CGD) relied on microbial catalase as a critical virulence factor. The argument was that, whereas CGD phagocytes lacked superoxide and hydrogen peroxide production, hydrogen peroxide-producing microbes would complement the defect in the CGD cell unless they also produced catalase to degrade their own hydrogen peroxide. In summary, CGD neutrophils and macrophages are defective in O2 - production. The phagosome gradually acquires molecules necessary for lysosomal fusion to produce the phagolysosome. Defects in lysosomal degradation typically result in intracellular accumulation of undegraded substrates, characterized by neurodegeneration without associated immunodeficiency. The classically activated macrophage is an IFN-γ -primed cell that recognizes, via specific cell surface receptors, microbes and their products.