Surfactant protein A down-regulates proinflammatory cytokine production evoked by Candida albicans in human alveolar macrophages and monocytes

Surfactant protein A (SP-A) has been implicated in the regulation of pulmon ary host defense and inflammatory events. We analyzed the impact of SP-A on the Candida albicans-induced cytokine response in human alveolar macrophag es (AM) and its precursor cells, the monocytes, which rapidly expand the al veolar mononuclear phagocyte pool under inflammatory conditions. Both recom binant human SP-A and natural canine SP-A were employed. SP-A dose-dependen tly down-regulated the proinflammatory cytokine response of AM and monocyte s to both viable and nonviable Candida, including TNF-alpha, IL-1 beta, mac rophage inflammatory protein-1 alpha, and monocyte chemoattractant protein- 1. In contrast, SP-A did not affect the baseline liberation of these cytoki nes, The release of the antiinflammatory cytokines IL-1 receptor antagonist and IL-6 was not inhibited by SP-A under baseline conditions and in respon se to fungal challenge. The inhibitory effect of SP-A on proinflammatory cy tokine release was retained upon reassembly of the apoprotein with natural surfactant lipids and in the presence of serum constituents, for mimicry of plasma leakage into the alveolar space. It was not reproduced by the homol ogous proteins complement component C1q and type TV collagen. It was indepe ndent of Candida-SP-A binding and phagocyte C1q receptor occupancy, but app arently demanded SP-A internalization by the mononuclear phagocytes, effect ing down-regulation of proinflammatory cytokine synthesis at the transcript ional level. We conclude that SP-A limits excessive proinflammatory cytokin e release in AM and monocytes confronted with fungal challenge in the alveo lar compartment. These data lend further credit to an important physiologic al role of SP-A in regulating alveolar host defense and inflammation.