title: Modulation of the complement system by human beta-defensin 2.
abstract: OBJECTIVE
  Human beta-defensin (HBD) and the complement system are two important innate immune mechanisms active against a broad range of burn and wound pathogens. However, excessive or uncontrolled complement activation, following thermal injury, contributes to tissue damage. Previous studies from our laboratory suggested a decreased expression of HBD-2 in burn wounds and its absence in burn blister fluid. Prior studies have demonstrated that human neutrophil peptide can bind to the C1q component of the complement system and prevent complement activation. The objective of this study was to determine whether HBD-1 and HBD-2 can also bind to the C1q component and modulate complement activity.
  
  
  METHODS
  The binding efficiency of HBD-1 and HBD-2 to the C1q component was determined by utilizing dot blot hybridization. The effect of HBD-2 on the activation of the complement system by the classical and alternative pathways was determined by CH50 and AP50 assays. In addition, the ability of HBD-1 and HBD-2 to inhibit C1q activity was predicted by a comparison with known C1q inhibitor peptide 2J in a DNAStar computer modeling study.
  
  
  RESULTS
  C1q binding to HBD-2 was strong, whereas C1q binding to HBD-1 was weak. HBD-2 inhibits the classical pathway significantly without affecting the alternative pathway. In addition, a computer modeling study also revealed structural homology of HBD-2 with known C1q inhibitory sequences of HBD-2.
  
  
  CONCLUSIONS
  HBD-2 inhibits the classical pathway. The replacement of missing defensin, a natural inhibitor of the complement system, may have a dual protective role not only as an antimicrobial agent but also in providing protection against uncontrolled activation of the complement system.
authors.affiliation: The Institute for Plastic and Reconstructive Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Satyanarayan
authors.initials: S
authors.lastname: Bhat
authors.forename: Yau-Hau
authors.initials: YH
authors.lastname: Song
authors.forename: Carl
authors.initials: C
authors.lastname: Lawyer
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Milner