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Febrile Neutropenia: Management Issues

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Emerging Issues and Controversies in Infectious Disease

Part of the book series: Emerging Infectious Diseases of the 21st Century ((EIDC))

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Neutrophils (granulocytes) are vital components of the effector mechanisms of the host defense. They represent part of the first-line defense against invading microbes (particularly bacteria and fungi), and are essential as part of the innate immune response. Neutrophils circulate as quiescent cells, and their main functions as phagocytic and bactericidal defenders are performed in tissues where microbial invasion occurs. The neutrophil microbicidal defense mechanisms for microbial killing can be either oxidative or non-oxidative. The principal oxidative killing of microbes is via the myeloperoxidase (MPO)–hydrogen peroxide (H2O2) pathway. The microbicidal products generated by the MPO–H2O2 pathway include hypo-chlorous acid, chlorination products, tyrosine radicals, and nitrogen intermediates.1 The neutrophils also produce a host of antimicrobial substances used to fight invading pathogens. These include (1) bacterial permeability-increasing (BPI) protein, which binds to lipopolysaccharide (LPS), with antimicrobial activity against gram-negative bacteria; (2) defensins, small amphipathic pore-forming antibacterial cationic peptides with broad antibacterial spectrum; (3) serine proteases (elastase, cathepsin G) with direct antibacterial activity, besides enzymatic function; (4) lysozyme which cleave peptoglycan-polymers of bacterial cell wall (i.e. gram-positive bacteria); (5) lactoferrin, iron chelator to sequester iron (essential for bacterial growth), but also the proteolytic fragments have direct bactericidal activity; (6) B2 integrins to mediate cellular adhesions and regulate phagocytosis; (7) cathelicidin protein (hcap-18), binds endotoxin, and has antibacterial activity against gram-positive bacteria as well.

The neutrophils also produce a host of antimicrobial substances used to fight invading pathogens. These include (1) bacterial permeability-increasing (BPI) protein, which binds to lipopolysaccharide (LPS), with antimicrobial activity against gram-negative bacteria; (2) defensins, small amphipathic pore-forming antibacterial cationic peptides with broad antibacterial spectrum; (3) serine proteases (elastase, cathepsin G) with direct antibacterial activity, besides enzymatic function; (4) lysozyme which cleave peptoglycan-polymers of bacterial cell wall (i.e. gram-positive bacteria); (5) lactoferrin, iron chelator to sequester iron (essential for bacterial growth), but also the proteolytic fragments have direct bactericidal activity; (6) B2 integrins to mediate cellular adhesions and regulate phagocytosis; (7) cathelicidin protein (hcap-18), binds endotoxin, and has antibacterial activityagainst gram-positive bacteria as well.

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  1. Professor of Medicine University of Toronto, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada

    I. W. Fong

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(2009). Febrile Neutropenia: Management Issues. In: Fong, I.W. (eds) Emerging Issues and Controversies in Infectious Disease. Emerging Infectious Diseases of the 21st Century. Springer, New York, NY. https://doi.org/10.1007/978-0-387-84841-9_8

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