Membrane molecules which trigger the production of interleukin‐1 and tumor necrosis factor‐α by lipopolysaccharide‐stimulated human monocytes

Abstract

We have investigated the role of the membrane molecules CD11/CD18 and CD14 whichmay mediate the binding of lipopolysaccharide (LPS) to human monocytes, in the induction of the production and release of interleukin (IL)‐1 and tumor necrosis factor‐α (TNF‐α) by LPS‐stimulated cells. Blockade of CD11a, CD11b and CD18 with saturating concentrations of specific mAb did not inhibit the releaseof cytokines from LPS‐stimulated monocytes. In contrast, inhibition of the release of IL‐1β and TNF‐α occurred in monocytes cultures that had been pretreated with either of two monoclonal antibodies (mAb) recognizing different epitopes on the CD14 molecule. The binding of LPS to CD14 has been previously shown to require serum factors. In the present study, we found that serum had an enhancing effect on the release of IL‐1 and TNF‐α from LPS‐stimulated cultures of normal human monocytes. The inhibitory effect of anti‐CD14 mAb was, however, observed in cultures performed in the presence or in the absence of serum, suggesting that triggering of IL‐1/TNF‐α release by CD14 is independent of LPS‐binding proteins or other serum proteins. IL‐1β and TNF‐α were also released from LPS‐stimulated cultures of monocytes from patients with paroxysmal nocturnal hemoglobinuria lacking expression of CD14. Thus, CD14 but notCD11/CD18 can trigger serum‐dependent and independent cytokine release from endotoxin‐stimulated normal human monocytes; CD14 is not, however, the only LPS receptor that is involved in the secretory response of endotoxin‐stimulated cells.