Neutrophils contain prolyl endopeptidase and generate the chemotactic peptide, PGP, from collagen.
Prolyl endopeptidase (PE), a protease that cleaves after proline residues in oligopeptides, is highly active in brain and degrades neuropeptides in vitro. We have recently demonstrated that PE, in concert with MMP's, can generate PGP (proline-glycine-proline), a novel, neutrophil chemoattractant, from collagen. In this study, we demonstrate that human peripheral blood neutrophils contain PE, which is constitutively active, and can generate PGP de novo from collagen after activation with LPS. This novel, pro-inflammatory role for PE raises the possibility of a self-sustaining pathway of neutrophilic inflammation and may provide biomarkers and therapeutic targets for diseases caused by chronic, neutrophilic inflammation.
O'Reilly
Philip J
PJ
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 5294-0005, USA. poreilly@uab.edu
Hardison
Matthew T
MT
Jackson
Patricia L
PL
Xu
Xin
X
Snelgrove
Robert J
RJ
Gaggar
Amit
A
Galin
F Shawn
FS
Blalock
J Edwin
JE
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002853:Chromatography, Liquid / Q000379:methods; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000302:isolation & purification / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000378:metabolism; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D009842:Oligopeptides; C113164:prolyl-glycyl-proline; D003094:Collagen; D011392:Proline; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases