Surfactant Protein A Suppresses Lipopolysaccharide-Induced IL-10 Production by Murine Macrophages

Abstract

Upon LPS exposure, mononuclear phagocytes produce TNF-α and IL-10, two cytokines with pro- and anti-inflammatory activities, respectively. We previously described that murine resident alveolar macrophages, which play a central 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 demonstrate that during lung inflammation induced by the intranasal administration 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 resident alveolar macrophages by an intratracheal instillation of liposome-encapsulated clodronate is followed by subsequent replenishment of the airspaces by mononuclear phagocytes. This is accompanied by the transient competence of cells for IL-10 production. The cell capacity to produce IL-10 is evident 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 synthesis by recently emigrating mononuclear phagocytes. We show that the surfactant protein A, an airspace protein that has known immunomodulatory activities, dramatically inhibits LPS-induced IL-10 formation by bone marrow-derived macrophages. These data show a difference between resident and inflammatory macrophages with respect to IL-10 synthesis. Moreover, this study highlights for the first time the inhibitory role of surfactant protein A in the anti-inflammatory activity of macrophages through inhibition of IL-10 production.

Sequential targeted deficiency of SP-A and -D leads to progressive alveolar lipoproteinosis and emphysema

“…The absolute increase in macrophage numbers and the level of MMP upregulation also appear to be greater in the SP-AD (Ϫ/Ϫ) mice compared with singly deficient SP-D null mice. This finding is consistent with a potential immunomodulatory role for SP-A on macrophage function (24,25,30), but further studies will be required with other markers of macrophage activation and in matched genetic backgrounds before firm conclusions can be drawn. The stereological analysis revealed significant increases in both mean linear intercept length and v of air spaces, clearly demonstrating air space enlargement in the SP-AD (Ϫ/Ϫ) mice.…”

Treponemal Phospholipids Inhibit Innate Immune Responses Induced by Pathogen-associated Molecular Patterns

“…The animals received humane care in accordance with our institutional guidelines and the legal requirements of Japan. Alveolar macrophages were obtained from mice using a modified technique of bronchoalveolar lavage (BAL) as described previously, with a slight modification (35). Elicited peritoneal macrophages were obtained from mice 3 days after intraperitoneal inoculation of 1.0 ml of 3% sterile Brewer's thioglycolate broth (BD Biosciences).…”

Monocyte and macrophage heterogeneity and Toll-like receptors in the lung

“…Most of the data related to the pro-inflammatory roles of alveolar macrophages have been obtained through in vitro studies in which the plasma membrane of alveolar macrophages has been cleared of surfactant lipids and proteins. The function of alveolar macrophages in vivo in alveolar spaces is potentially modulated by their continuous interactions with the lipid and proteins of the surfactant, which is a critical part of their microenvironment (Henning et al 2008;Pastva et al 2007;Reidy and Wright 2003;Salez et al 2001). Surfactant proteins are known to modulate the expression of inflammatory mediators by the alveolar macrophages by altering the functions of Toll-like receptors (TLRs) in order to dampen their potential for rapid activation in response to agonists (Liu et al 2010).…”