Serum amyloid A binds specific extracellular matrix glycoproteins and induces the adhesion of resting CD4+ T cells.
Serum amyloid A (SAA), a prototypic acute phase protein reactant, exists naturally in the serum of healthy individuals. However, the levels of SAA in serum and its presence in sites of inflammation increase during certain chronic diseases associated with a local elevation of cytokine concentrations. Although the chemical structure of SAA is defined, its putative immunologic role(s) is still obscure. Nevertheless, it has been shown that 1) SAA acts as a chemoattractant and regulator of the migration of monocytes, polymorphonuclear cells, and T lymphocytes through endothelial cell monolayers; and 2) SAA and its proteolytically degraded N-terminal amyloid A fragment contain an extracellular matrix (ECM)-related cell adhesion epitopes. Herein, we examined whether SAA can associate with specific ECM moieties, and whether immobilized SAA-ECM complexes affect T lymphocyte adhesion. Radiolabeled human rSAA ([125I]rSAA) interacted avidly (Kd = 10(-9) M) and transiently with intact ECM, laminin, and vitronectin, but not with fibronectin or collagen type II. The binding of [125I]rSAA to ECM and laminin was inhibited by unlabeled rSAA and by the AA fragment, but not by the C-terminal portion of SAA (amino acid residues 2-82 and 77-104, respectively). Upon interactions with SAA or amyloid A, immobilized ECM, laminin, and vitronectin induced the adhesion of resting human CD4+ T cells in an apparently beta 1-integrin-mediated manner. Thus, the ECM appears to serve as a temporary anchorage site for SAA and amyloid A, and these ECM-complexed molecules seem to be involved in regulating the recruitment and accumulation of immunocytes in extravascular inflammatory compartments.
Preciado-Patt
L
L
Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Hershkoviz
R
R
Fridkin
M
M
Lider
O
O
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000494:pharmacology; D005353:Fibronectins / Q000737:chemistry; D006801:Humans; D016023:Integrins / Q000502:physiology; D007399:Interphase / Q000187:drug effects; D007797:Laminin / Q000737:chemistry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000737:chemistry / Q000494:pharmacology*; D019096:Vitronectin / Q000737:chemistry
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D010446:Peptide Fragments; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D019096:Vitronectin