Immunosuppression by a peptide from the gelatin binding domain of human fibronectin

Circulating immunosuppressive peptides are found in conjunction with elevated protease activity in injured patients' serum. Previous work suggests that fibronectin may be a source of these peptides. Elastase-generated fibronectin degradation products were chromatographically separated and assessed for immunosuppressive capacity in the neutrophil chemotaxis and mixed lymphocyte reaction bioassays. The suppressive fibronectin degradation products fraction 22 inhibited chemotaxis by 53% (P less than 0.01) and mixed lymphocyte reaction by 41% (P less than 0.001). Incubation of the suppressive fraction 22 with gelatin, neuraminidase, or anti-SAP (suppressor active peptide) antibody reverses the chemotaxis inhibition to control values. These results indicate that an elastase-generated fragment of fibronectin, which potently inhibits neutrophil and lymphocyte activity, is located within the sialated gelatin binding portion of the molecule. Immunosuppression reversal by anti-SAP antibody, and the requirement for sialic acid, suggests similarity between fraction 22 and SAP, although other explanations are plausible. This peptide fragment from fibronectin may impact on the clinical immunosuppression seen in patients following severe trauma.