Cathelicidin LL-37: LPS-neutralizing, pleiotropic peptide.
Human organism, constantly exposed to a large variety of pathogenic microorganisms and their products, such as lipopolysaccharide (LPS), developed innate immunity as a first line of defence. One of the compartments of our organism well equipped with these defence mechanisms is the respiratory system. The cells lining the airways respond to the presence of virulent microorganisms by producing natural antimicrobial peptides, including the only member of the cathelicidins family found to date in humans, peptide LL-37. LL-37 is a small peptide of 37 amino acid residues. The peptide, in addition to its bactericidal effect, plays numerous roles in inflammatory and tissue remodelling processes. It stimulates angiogenesis, induces proliferation of lung epithelial cells, accelerates wound closure of the airway epithelium, and provokes cytokine release (e.g. IL-8) and cell migration. LL-37 is also able to neutralize LPS, a heteropolymer associated with organic dust, produced by Gram-negative bacteria. LPS (commonly referred to as endotoxin) plays an important role in pathogenesis of many respiratory diseases caused by organic dust, including organic dust toxic syndrome and chronic illnesses such as chronic obstructive pulmonary disease (COPD), asthma or allergic alveolitis (hypersensitivity pneumonitis). LPS is a strong pro-inflammatory stimulus, inducing in respiratory airways expression of antimicrobial peptides, including LL-37, which is in turn a potent LPS-neutralizing factor. The article discusses the complex interplay between endotoxin and the LPS-neutralizing, pleiotropic peptide LL-37 in pathogenic mechanisms of lung diseases, with regard to closer perspectives of using LL-37 and its derivatives as therapeutic agents.
Golec
Marcin
M
Department of Occupational Biohazards, Institute of Agricultural Medicine, Jaczewskiego 2, 20-090 Lublin, Poland. msgolec@yahoo.com
D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008171:Lung Diseases / Q000276:immunology*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D054804:Cathelicidins