Degradation of extracellular matrix components by defined proteinases from the greenbottle larva Lucilia sericata used for the clinical debridement of non-healing wounds

Br J Dermatol. 2003 Jan;148(1):14-23. doi: 10.1046/j.1365-2133.2003.04935.x.

Abstract

Background: Larvae of the greenbottle fly Lucilia sericata are used routinely for the clinical treatment of difficult necrotic and infected wounds. Degradation by proteinases contained in larval excretory/secretory (ES) products is thought to contribute to wound debridement by removal of dead tissue. However, proteinase activity may also affect host tissue remodelling processes.

Objectives: To identify proteolytic enzymes derived from L. sericata ES products with activities against fibrin and extracellular matrix (ECM) components.

Methods: Larval proteinase activities were assayed in vitro using class-specific substrates and inhibitors. Their action against fibrin and ECM components was examined using sodium dodecyl sulphate-polyacrylamide gel electrophoresis.

Results: Three classes of proteolytic enzyme were detected in the secretions using fluorescein isothiocyanate-labelled casein as a model substrate. The predominant activity belonged to serine proteinases (pH optima 8-9) of two different subclasses (trypsin-like and chymotrypsin-like), with a weaker aspartyl proteinase (pH 5) and a metalloproteinase (pH 9) with exopeptidase characteristics also present. Using skin-relevant ECM components as substrates L. sericata ES products solubilized fibrin clots and degraded fibronectin, laminin and acid-solubilized collagen types I and III. Hydrolysis of ECM macromolecules was inhibited by preincubating ES products with phenylmethylsulphonyl fluoride but not 4-amidinophenylmethylsulphonyl fluoride, indicating that degradation was due to the 'chymotrypsin-like' serine proteinase.

Conclusions: These data suggest that a combination of L. sericata ES proteinases involving chymotrypsin-like and trypsin-like activities could potentially influence wound healing events when maggots are introduced into necrotic and infected wounds, with the chymotrypsin-like activity involved in the remodelling of ECM components.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chymotrypsin / metabolism
  • Collagen / metabolism
  • Diptera / enzymology*
  • Electrophoresis, Polyacrylamide Gel
  • Endopeptidases / metabolism
  • Endopeptidases / pharmacology*
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / metabolism
  • Fibrin / metabolism
  • Fibronectins / metabolism
  • Hydrogen-Ion Concentration
  • Laminin / metabolism
  • Larva / enzymology
  • Serine Endopeptidases / metabolism
  • Trypsin / metabolism
  • Wound Healing / physiology

Substances

  • Fibronectins
  • Laminin
  • Fibrin
  • Collagen
  • Endopeptidases
  • Serine Endopeptidases
  • Chymotrypsin
  • Trypsin