Serum-induced potentiation of tumor necrosis factor alpha production by human monocytes in response to staphylococcal peptidoglycan: involvement of different serum factors.

Peptidoglycan from a Staphylococcus epidermidis strain, isolated from a patient with septicemia, was preincubated with human serum. This mixture was then investigated for its potency to induce tumor necrosis factor (TNF) secretion by human blood monocytes. TNF was measured in the supernatants by using a bioassay and/or an enzyme-linked immunosorbent assay specific for TNF alpha (TNF-alpha). Although earlier studies indicated that staphylococcal peptidoglycan alone is a relatively poor stimulator of TNF-alpha production, the present study shows that human serum highly potentiates peptidoglycan-induced TNF-alpha release by human monocytes. In the presence of serum and in the low-dose range, peptidoglycan was almost as potent as endotoxin. At high peptidoglycan concentrations, monocytes showed an extremely high TNF-alpha response, but again only in the presence of serum. At low peptidoglycan doses, the stimulatory effect of serum was abrogated by heat treatment or depleting serum of complement components C1 and C3/C4, which suggests a role for the classical complement pathway. At high doses of peptidoglycan, the serum stimulatory effect depended mainly on immunoglobulin G.