Roles of serum in innate immune responses of human leukocytes to synthetic lipopeptide.

Tripalmitoyl-S-glyceryl-l-Cys-Ser-(Lys) (PamCSK) is a highly conserved molecular motif found in various classes of lipoproteins. The requirement for leukocyte to respond to synthetic PamCSK were studied. PamCSK primed neutrophils for a respiratory burst in a serum-dependent manner. PamCSK upregulated CD11b, CD14, and cytochrome b, and downregulated Leu-8. Treatment of neutrophils with anti-CD14 antibodies and treatment of serum with anti-LPS binding protein (LBP) antibodies resulted in the inhibition of priming for respiratory burst by PamCSK. It should be noted that LBP could not replicate the effects of serum in priming of neutrophils for respiratory burst by PamCSK. Serum LBP bound to immobilized PamCSK. PamCSK induced the interleukin-8 (IL-8) production by leukocytes in a serum-dependent manner. Further, PamCSK-induced priming of neutrophils for respiratory burst was not inhibited by the LPS antagonists LA-14-PP, Rhodobacter sphaeroides LPS, or E5531, and PamCSK-induced IL-8 production by leukocytes was not affected by LPS antagonist, E5531, indicating that PamCSK was recognized by a different receptor than LPS. Thus, PamCSK and LPS had similar biological activities and similar requirement to act on leukocytes, but were recognized by different receptors. Serum in the action of PamCSK on leukocytes was not replicated by LBP, suggesting that PamCSK might be disaggregated by serum to result in the activation of leukocytes.