Mice lacking serum amyloid P component do not necessarily develop severe autoimmune disease

Serum amyloid P component (SAP) is a major acute-phase reactant in mice. Re cently, it was reported that SAP-deficient mice spontaneously developed ant inuclear antibodies and severe glomerulonephritis. Because the SA-P-deficie nt mice we generated display no obvious phenotypic abnormalities, we invest igated whether our SAP-deficient mice would also spontaneously develop auto immune responses. In accordance with the report, our mice produced high tit ers of antinuclear antibody but did not develop severe glomerulonephritis. On the other hand, it was recently reported that SAP bound to gram-negative bacteria via lipopolysaccharide (LPS) prevented LPS-mediated activation of a classical complement pathway. Thus, we asked if SAP-deficient mice would show altered responses to an intraperitoneal injection of LPS from Salmone lla typhimirium. SAP-deficiency did afford resistance to lethality induced by high-dose LPS. Our experiments clearly showed that contrary to documente d data, SAP-deficient mice do not develop serious autoimmune disease and we suggest that SAP has a critical role in LPS toxicity. (C) 2001 Academic Pr ess.