Deactivation of the respiratory burst of human and murine macrophages by lipopolysaccharide is a receptor mediated effect independent from autocrine mechanisms

Abstract

Endotoxin blunts secretion of reactive oxygen intermediates by macrophages. Because transforming growth factor β (TGFβ) or interleukin 10 (IL-10) were shown to deactivate macrophages, and are secreted by macrophages in response to LPS, we sought for autocrine mechanisms of macrophage deactivation by endotoxin. TGFβ did not deactivate the respiratory burst of human blood-derived and resident or thioglycollate-induced murine peritoneal macrophages. According to previous reports, suppression of H202 secretion by TGFβ was restricted to periodate-elicited murine peritoneal macrophages.

In contrast to TGFβ, IL-10 deactivated systems producing reactive oxygen intermediates in human blood-derived human macrophages, but neither anti-TGFβ1 nor anti-IL-10 antibodies restored LPS-mediated deactivation of macrophages.

Supernatants from LPS-treated human blood-derived macrophages could not confer deactivation to homologous macrophages.

Deactivation by LPS required the presence of serum proteins and appeared to be mediated by the CD14 antigen-related LPS receptor, because anti-CD14 antibody and IL-4, which downregulates CD14, antagonized the LPS effect.

Taken together, these observations indicate that the suppressive effect of LPS on the respiratory burst of macrophages is lipid A receptor-dependent, and results in a direct deactivation response of the cell without mediation by autocrine mechanisms.