The serpin-enzyme complex (SEC) receptor mediates the neutrophil chemotactic effect of alpha-1 antitrypsin-elastase complexes and amyloid-beta peptide
- PMID: 1325993
- PMCID: PMC329978
- DOI: 10.1172/JCI115934
The serpin-enzyme complex (SEC) receptor mediates the neutrophil chemotactic effect of alpha-1 antitrypsin-elastase complexes and amyloid-beta peptide
Abstract
The serpin-enzyme complex (SEC) receptor mediates catabolism of alpha 1-antitrypsin (alpha 1-AT)-elastase complexes and increases in synthesis of alpha 1-AT in cell culture. The SEC receptor recognizes a pentapeptide domain on alpha 1-AT-elastase complexes (alpha 1-AT 370-374), and the same domain in several other serpins, amyloid-beta 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-beta peptide. In this study, we examined the possibility that the SEC receptor mediates the previously described neutrophil chemotactic activity of alpha 1-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 alpha 1-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-beta 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 alpha 1-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-beta 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.
Similar articles
-
Identification of a serpin-enzyme complex receptor on human hepatoma cells and human monocytes.Proc Natl Acad Sci U S A. 1990 May;87(10):3753-7. doi: 10.1073/pnas.87.10.3753. Proc Natl Acad Sci U S A. 1990. PMID: 2160076 Free PMC article.
-
Cross-competition for binding of alpha 1-antitrypsin (alpha 1 AT)-elastase complexes to the serpin-enzyme complex receptor by other serpin-enzyme complexes and by proteolytically modified alpha 1 AT.J Biol Chem. 1993 Jan 25;268(3):1886-93. J Biol Chem. 1993. PMID: 8380581
-
Amyloid-beta peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor.J Biol Chem. 1991 Nov 15;266(32):21897-902. J Biol Chem. 1991. PMID: 1718986
-
Cefoperazone prevents the inactivation of alpha(1)-antitrypsin by activated neutrophils.Antimicrob Agents Chemother. 1999 Sep;43(9):2307-10. doi: 10.1128/AAC.43.9.2307. Antimicrob Agents Chemother. 1999. PMID: 10471586 Free PMC article. Review.
-
Heterogeneity of human neutrophil and monocyte chemotactic responsiveness.Surv Immunol Res. 1983;2(2):145-9. doi: 10.1007/BF02918573. Surv Immunol Res. 1983. PMID: 6316459 Review. No abstract available.
Cited by
-
Oxidized {alpha}1-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: potential role in emphysema.Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L388-400. doi: 10.1152/ajplung.90373.2008. Epub 2009 Jun 12. Am J Physiol Lung Cell Mol Physiol. 2009. PMID: 19525388 Free PMC article.
-
Migration of blood cells to β-amyloid plaques in Alzheimer's disease.Exp Gerontol. 2015 May;65:8-15. doi: 10.1016/j.exger.2015.03.002. Epub 2015 Mar 6. Exp Gerontol. 2015. PMID: 25752742 Free PMC article. Review.
-
Clathrin pit-mediated endocytosis of neutrophil elastase and cathepsin G by cancer cells.J Biol Chem. 2012 Oct 12;287(42):35341-35350. doi: 10.1074/jbc.M112.385617. Epub 2012 Aug 22. J Biol Chem. 2012. PMID: 22915586 Free PMC article.
-
Gene transfer into hepatoma cell lines via the serpin enzyme complex receptor.Am J Physiol. 1997 Aug;273(2 Pt 1):G545-52. doi: 10.1152/ajpgi.1997.273.2.G545. Am J Physiol. 1997. PMID: 9277436 Free PMC article.
-
Enhanced tumor growth and invasiveness in vivo by a carboxyl-terminal fragment of alpha1-proteinase inhibitor generated by matrix metalloproteinases: a possible modulatory role in natural killer cytotoxicity.Am J Pathol. 1999 Feb;154(2):457-68. doi: 10.1016/s0002-9440(10)65292-3. Am J Pathol. 1999. PMID: 10027404 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources