LYSOZYME BINDS TO ELASTIN AND PROTECTS ELASTIN FROM ELASTASE-MEDIATEDDEGRADATION

Lysozyme has been shown to be associated with damaged elastic fibers i n many tissues and organs. To better characterize this interaction, bi nding of lysozyme to elastin was studied using solution-based binding assays. Under physiologic conditions, radio-labeled lysozyme bound spe cifically to elastin in a time- and concentration-dependent manner. Bi nding was reversible and was inhibited by unlabeled human and hen lyso zyme but not by other proteins. Lysozyme had no elastolytic activity a s assessed by a standard tritium-release assay, but, importantly, prev ented the proteolytic degradation of elastin by human leukocyte elasta se, pancreatic elastase, thermolysin, and Pseudomonas elastase. A stri king feature of lysozyme's anti-elastase activity was that it did not function in the classical sense of inhibiting directly the enzymatic a ctivity of the protease. Instead, by binding to elastin, lysozyme prev ented the protease from interacting with the elastin substrate in ways that normally favor proteolysis. These results show that lysozyme bin ds to the elastin component of elastic fibers and that this interactio n has important biological consequences for elastic fiber degradation. By preventing degradation of elastin, lysozyme can function as an imp ortant natural inhibitor that exerts a protective effect on elastic fi bers at sites of tissue injury.