Inhibition of cell adhesion to glycoproteins of the extracellular matrix by peptides corresponding to serum amyloid A. Toward understanding the physiological role of an enigmatic protein.
Synthetic peptides related to amino acid residues 29-42 of human serum amyloid A (SAA), Tyr-Ile-Gly-Ser-Asp-Lys-Tyr-Phe-His-Ala-Arg-Gly-Asn-Tyr, were found to inhibit the adhesion of human T-lymphocytes and of mouse M4 melanoma cells to surfaces coated with the major cell adhesive glycoproteins of the extracellular matrix, laminin or fibronectin. Correspondingly inhibitory activity was manifested by the entire 14-residue peptide, by its YIGSD laminin-related domain, and by RGN, the fibronectin-related domain. Intact recombinant SAA (rSAA) and its 1-76 fragment, an amyloid A (AA) protein, also inhibited cell adhesion. The peptides did not inhibit collagen and ADP-induced aggregation of human platelets. Proteolysis of SAA by lysosomal enzymes originating from human neutrophils led to generation of specific peptide segments some of which pertain to the 29-42 domain. It is suggested that the acute-phase protein SAA might be involved, either directly or via its peptide fragments, in inhibition of inflammatory reactions or metastatic processes which depend on integrin and possibly other extracellular-matrix-specific receptors mediated specific recognition and interactions with immobilized components of blood-vessel walls.
Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel.
L
L
Preciado-Patt
D
D
Levartowsky
M
M
Prass
R
R
Hershkoviz
O
O
Lider
M
M
Fridkin
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D010455:Peptides; D000685:Serum Amyloid A Protein