eTopic 23.1 Cathelicidins
Cathelicidins form a large family of cationic antimicrobial peptides expressed in many species. Their structure, however, differentiates them from defensins. The only human cathelicidin is hCAP18/LL-37, which has similar biology to defensins and also plays important roles in mucosal defense. Like the defensins, hCAP18/LL-37 has a broad spectrum of antimicrobial activity and many immunomodulatory effects.
hCAP18 can be found in its inactive state in the granules of NK cells of the immune system. It has also been found in the mucosal surfaces of the mouth, the lung and in broncho-alveolar lavage fluid.
Initially synthesized as inactive precursor proteins, the human cathelicidin hCAP18 contains a 100-amino-acid N-terminal domain called cathelin that is attached to a smaller antimicrobial domain at the N terminus. Extracellular proteolytic cleavage of the large proprotein releases the now-active antimicrobial peptide (LL-37). As with the defensins, most cathelicidins are thought to function by assembling within bacterial membranes, where they disrupt membrane integrity. Some nonhuman cathelicidins, however, penetrate to the cell interior and disrupt protein synthesis. Their immunomodulary functions include epithelial wound repair and activation of chemokine secretion.