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Chapter 8 : Defensins and Cathelicidins: Antimicrobial Peptide Effectors of Mammalian Innate Immunity
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This chapter centers on antimicrobial peptides, effector molecules that generally act by disrupting microbial membranes. When human neutrophils ingest Salmonella enterica serovar Typhimurium in the presence of radioactive iodide, defensins are the most abundant radioiodinated polypeptides in phagocytic vacuoles. Since iodination is produced by the neutrophil’s myeloperoxidase-hydrogen peroxide system, iodinated defensins provide evidence that the neutrophil’s oxidative and nonoxidative systems operate concurrently within the phagosome. Presumably, adverse consequences from the lack of neutrophil defensins in these species are mitigated by the presence of other antimicrobial effector mechanisms, such as NADPH oxidase, inducible nitric oxide synthase, cathelicidins, serprocidins, and other antimicrobial polypeptides. The only known human cathelicidin has been designated hCAP18 or FALL39/LL-37 by the three groups that described its cDNA, gene and peptide forms. Unlike defensins, which are stored in their mature form in the granules of neutrophils, hCAP18/LL-37 is stored as a 16-kDa (140-aminoacid) proform. Individual peptides differ in their antimicrobial spectrum, and early evidence suggests that they sometimes act synergistically with each other or with larger antimicrobial polypeptides. At sites that are more distant from the infected or inflamed locus, lower concentrations of defensins may act as signaling molecules, similarly to chemokines.