PMID:14978112

Citation	Murakami, M, Lopez-Garcia, B, Braff, M, Dorschner, RA and Gallo, RL (2004) Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J. Immunol. 172:3070-7
Abstract	The production of antimicrobial peptides and proteins is essential for defense against infection. Many of the known human antimicrobial peptides are multifunctional, with stimulatory activities such as chemotaxis while simultaneously acting as natural antibiotics. In humans, eccrine appendages express DCD and CAMP, genes encoding proteins processed into the antimicrobial peptides dermcidin and LL-37. In this study we show that after secretion onto the skin surface, the CAMP gene product is processed by a serine protease-dependent mechanism into multiple novel antimicrobial peptides distinct from the cathelicidin LL-37. These peptides show enhanced antimicrobial action, acquiring the ability to kill skin pathogens such as Staphylococcus aureus and Candida albicans. Furthermore, although LL-37 may influence the host inflammatory response by stimulating IL-8 release from keratinocytes, this activity is lost in subsequently processed peptides. Thus, a single gene product encoding an important defense molecule alters structure and function in the topical environment to shift the balance of activity toward direct inhibition of microbial colonization.
Links	PubMed
Keywords	Adjuvants, Immunologic/isolation & purification; Adjuvants, Immunologic/secretion; Adjuvants, Immunologic/toxicity; Amino Acid Sequence; Antimicrobial Cationic Peptides/biosynthesis; Antimicrobial Cationic Peptides/isolation & purification; Antimicrobial Cationic Peptides/secretion; Antimicrobial Cationic Peptides/toxicity; Cathelicidins; Cells, Cultured; Humans; Immunity, Innate; Interleukin-8/secretion; Keratinocytes/immunology; Keratinocytes/secretion; Keratins/biosynthesis; Keratins/isolation & purification; Keratins/secretion; Keratins/toxicity; Molecular Sequence Data; Peptides/isolation & purification; Peptides/metabolism; Peptides/secretion; Peptides/toxicity; Protein Processing, Post-Translational/immunology; Sequence Analysis, Protein; Skin/immunology; Skin/microbiology; Skin/secretion; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sweat/immunology; Sweat/microbiology; Sweat/secretion
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:CAMP	involved_in	GO:2000484: positive regulation of interleukin-8 secretion	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(CL:0000312)	Seeded From UniProt	complete
HUMAN:CAMP	involved_in	GO:0050829: defense response to Gram-negative bacterium	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAMP	involved_in	GO:0001878: response to yeast	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAMP	involved_in	GO:0019732: antifungal humoral response	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAMP	involved_in	GO:0050830: defense response to Gram-positive bacterium	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAMP	involved_in	GO:0019731: antibacterial humoral response	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAMP	involved_in	GO:0045087: innate immune response	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAMP	part_of	GO:0005615: extracellular space	ECO:0000314: direct assay evidence used in manual assertion		C	part_of:(UBERON:0001089)	Seeded From UniProt	complete
HUMAN:CAMP	involved_in	GO:0061844: antimicrobial humoral immune response mediated by antimicrobial peptide	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:DCD	part_of	GO:0005615: extracellular space	ECO:0000314: direct assay evidence used in manual assertion		C	part_of:(UBERON:0001089)	Seeded From UniProt	complete

References

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