SERUM AMYLOID A BINDS SPECIFIC EXTRACELLULAR-MATRIX GLYCOPROTEINS ANDINDUCES THE ADHESION OF RESTING CD4(-CELLS() T)

Serum amyloid A (SAA), a prototypic acute phase protein reactant, exis ts naturally in the serum of healthy individuals. However, the levels of SAA in serum and its presence in sites of inflammation increase dur ing certain chronic diseases associated with a local elevation of cyto kine 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 proteolytical ly degraded N-terminal amyloid A fragment contain an extracellular mat rix (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 rSA A ([I-125]rSAA) interacted avidly (K-d = 10(-9) M) and transiently wit h intact ECM, laminin, and vitronectin, but not with fibronectin or co llagen type II. The binding of [I-125]rSAA to ECM and laminin was inhi bited by unlabeled rSAA and by the AA fragment, but not by the C-termi nal portion of SAA (amino acid residues 2-82 and 77-104, respectively) . Upon interactions with SAA or amyloid A, immobilized ECM, laminin, a nd 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 the se ECM-complexed molecules seem to be involved in regulating the recru itment and accumulation of immunocytes in extravascular inflammatory c ompartments.