The serpin-enzyme complex (SEC) receptor mediates the neutrophil chemotactic effect of α-1 antitrypsin-elastase complexes and amyloid-β peptide

Gregg Joslin, Gail L. Griffin, Anna M. August, Steve Adams, Robert J. Fallen, Robert M. Senior, David H. Perlmutter

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63 Scopus citations


The serpin-enzyme complex (SEC) receptor mediates catabolism of α1-antitrypsin (α1-AT)-elastase complexes and increases in synthesis of α1-AT in cell culture. The SEC receptor recognizes a pentapeptide domain on α1-AT-elastase complexes (α1-AT 370-374), and the same domain in several other serpins, amyloid-β peptide, substance P, and other tachykinins. Thus, it has also been implicated in the biological properties of these ligands, including the neurotoxic effect of amyloid-β peptide. In this study, we examined the possibility that the SEC receptor mediates the previously described neutrophil chemotactic activity of α1-AT-elastase complexes, and whether the other ligands for the SEC receptor have neutrophil chemotactic activity. The results show that 125I-peptide 105Y (based on α1-AT 359-374) binds specifically and saturably to human neutrophils, and the characteristics of this binding are almost identical to that of monocytes and hepatoma-derived hepatocytes. Peptide 105Y and amyloid-β peptide mediate chemotaxis for neutrophils with maximal stimulation at 1-10 nM. Mutant or deleted forms of peptide 105Y, which do not bind to the SEC receptor, have no effect. The neutrophil chemotactic effect of α1-AT-elastase complexes is blocked by antiserum to peptide 105Y and by antiserum to the SEC receptor, but not by control antiserum. Preincubation of neutrophils with peptide 105Y or substance P completely blocks the chemotactic activity of amyloid-/? peptide, but not that of FMLP. These results, therefore, indicate that the SEC receptor can be modulated by homologous desensitization and raise the possibility that pharmacological manipulation of this receptor will modify the local tissue response to inflammation /injury and the neuropathologic reaction of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)1150-1154
Number of pages5
JournalJournal of Clinical Investigation
Issue number3
StatePublished - Jan 1 1992



  • Alzheimer's disease
  • Down's syndrome
  • Inflammation
  • Protease inhibitors
  • Serpins

ASJC Scopus subject areas

  • Medicine(all)

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