Summary
Serum amyloid A (SAA), an acute-phase reactant, exists naturally as a minor protein in the sera of healthy individuals. However, its levels in sera are increased markedly during various transient and chronic inflammatory diseases, often concomitantly with accumulation at inflicted sites. SAA is synthesized mainly in the liver following the synergistic action of cytokines, mainly tumor necrosis factor-α (TNF-α) and interleukin-1 and-6 (IL-1 and IL-6). It was already shown by us that upon interaction with SAA or amyloid A (AA), the extracellular matrix (ECM) and laminin induced the adhesion of resting human CD4+ T-cells in an apparently β1-integrin-mediated manner. Herein we have shown that the SAA-ECM complex modulates the regulation of cytokine synthesis by human T-lymphocytes. The SAA-ECM complex dramatically enhanced the release of TNF-α by human T-cells in a dose-dependent manner, reaching its maximal effect in the presence of 100 μM recombinant SAA. The SAA domain, responsible for the enhanced release of TNF-α by human T-lymphocytes, is apparently the amyloid A protein (AA, i.e. SAA2-82). Specifically, TNF-α enhanced secretion is mediated through intimate interactions of SAA/AA, with laminin. Thus, the ECM serving as a temporary anchorage site for SAA and AA seems to be involved in regulating TNF-α secretion and the recruitment and accumulation of immunocytes in extravascular, inflammatory compartments.
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Abbreviations
- AA:
-
amyloid A
- ECM:
-
extracellular matrix
- Fn:
-
fibronectin
- Ln:
-
laminin
- PHA:
-
phytohemoagglutinin
- SAA:
-
serum amyloid A
- TNF-α:
-
tumor necrosis factor-α
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Preciado-Patt, L., Cahalon, L., Hershkovitz, R. et al. Serum amyloid A complexed with extracellular matrix induces the secretion of tumor necrosis factor-α by human T-lymphocytes. Lett Pept Sci 5, 349–355 (1998). https://doi.org/10.1007/BF02443485
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DOI: https://doi.org/10.1007/BF02443485