Identification of a serpin-enzyme complex receptor on human hepatoma cells and human monocytes

Journal Article · Tue May 01 04:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.10.3753· OSTI ID:5322988

Perlmutter, D H; Fallon, R J ^[1]; Glover, G I; Rivetna, M; Schasteen, C S ^[2]

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1. Washington Univ. School of Medicine, St. Louis, MO (USA)
2. Monsanto Corporation, Chesterfield, MO (USA)

Formation of the covalently stabilized complex of {alpha}{sub 1}-antitrypsin ({alpha}{sub 1}AT) with neutrophil elastase, the archetype of serine proteinase inhibitor serpin-enzyme complexes, is associated with structural rearrangement of the {alpha}{sub 1}-AT molecule and hydrolysis of a reactive-site peptide bond. An {approx}4-kDa carboxyl-terminal cleavage fragment is generated. {alpha}{sub 1}-AT-elastase complexes are biologically active, possessing chemotactic activity and mediating increases in expression of the {alpha}{sub 1}-AT gene in human monocytes and macrophages. This suggested that structural rearrangement of the {alpha}{sub 1}-AT molecule, during formation of a complex with elastase, exposes a domain that is recognized by a specific cell surface receptor or receptors. To test this hypothesis, the known three-dimensional structure of {alpha}{sub 1}-AT and comparisons of the primary structures of the serpins were used to select a potentially exteriorly exposed and highly conserved region in the complexed form of {alpha}{sub 1}-AT as a candidate ligand. The results show that peptide 105Y inhibits binding of {sup 125}I-labeled {alpha}{sub 1}-AT-elastase complexes. Thus, these studies demonstrate an abundant, relatively high-affinity cell surface receptor which recognizes serpin-enzyme complexes (SEC receptor). This receptor is capable of modulating the production of at least one of the serpins, {alpha}{sub 1}-AT.

• OSTI ID: 5322988
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 87:10; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
BETA DECAY RADIOISOTOPES
BIODEGRADATION
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHEMICAL REACTIONS
CONNECTIVE TISSUE
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ENZYME INHIBITORS
ENZYMES
GLYCOPROTEINS
HEPATOMAS
HYDROLASES
INACTIVATION
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
MATERIALS
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
MONOCYTES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PROTEINS
RADIOISOTOPES
RADIORECEPTOR ASSAY
RECEPTORS
SERINE PROTEINASES
TISSUES
TRACER TECHNIQUES