Surfactant protein A suppresses lipopolysaccharide-induced IL-10 production by murine macrophages

Upon LPS exposure, mononuclear phagocytes produce TNF-alpha and IL-10, two cytokines with pro- and anti-inflammatory activities, respectively. We prev iously described that murine resident alveolar macrophages, which play a ce ntral role in the immunosurveillance of the lung alveoli, do not synthesize IL-10 in vivo or in vitro when exposed to LPS. In the present report we de monstrate that during lung inflammation induced by the intranasal administr ation of LPS, bronchoalveolar cells collected between days 3 and 5 are able to synthesize IL-10 when exposed to LPS. We also show that depletion of re sident alveolar macrophages by an intratracheal instillation of liposome-en capsulated clodronate is followed by subsequent replenishment of the airspa ces by mononuclear phagocytes. This is accompanied by the transient compete nce of cells for IL-10 production. The cell capacity to produce IL-10 is ev ident up to 3 days and then decreases. This led us to hypothesize that the alveolar environment contains a down-regulator of LPS-induced IL-10 synthes is by recently emigrating mononuclear phagocytes. We show that the surfacta nt protein A, an airspace protein that has known immunomodulatory activitie s, dramatically inhibits LPS-induced IL-10 formation by bone marrow-derived macrophages. These data show a difference between resident and inflammator y macrophages with respect to IL-10 synthesis. Moreover, this study highlig hts for the first time the inhibitory role of surfactant protein A in the a nti-inflammatory activity of macrophages through inhibition of IL-10 produc tion.