ENZYMOLOGY
Hydrolysis of a Broad Spectrum of Extracellular Matrix Proteins by Human Macrophage Elastase*

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Macrophage elastase (ME) was originally named when metal-dependent elastolytic activity was detected in conditioned media of murine macrophages. Subsequent cDNA cloning of the mouse and human enzyme demonstrated that ME is a distinct member of the matrix metalloproteinase family. To date, the catalytic parameters that describe the hydrolysis of elastin by ME have not been quantified and its activity against other matrix proteins have not been described. In this report, we have examined the action of purified recombinant human ME (rHME), produced in Escherichia coli, on elastin and other extracellular matrix proteins. On a molar basis, rHME is approximately 30% as active as human leukocyte elastase in solubilizing elastin. rHME also efficiently degrades α1-antitrypsin (α1-AT), the primary physiological inhibitor of human leukocyte elastase. In addition, rHME efficiently degrades fibronectin, laminin, entactin, type IV collagen, chondroitan sulfate, and heparan sulfate. These results suggest that HME may be required for macrophages to penetrate basement membranes and remodel injured tissue during inflammation. Moreover, abnormal expression of HME may contribute to destructive processes such as pulmonary emphysema and vascular aneurysm formation. To further understand the specificity of HME, the initial cleavage sites in α1-AT have been determined. In addition, the hydrolysis of a series of synthetic peptides with different P′1residues has been determined. rHME can accept large and small amino acids at the P′1 site, but has a preference for leucine.

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This work was supported by United States Public Health Service Grants HL50472, HL55160 and HL54853 (to S. D. S.), GM27939 (to H. E. V. W.), and by the American Lung Association Fellowship Award (to T. J. G.) and a Career Investigator Award (to S. D. S.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.