title: Surfactant protein A binds flagellin enhancing phagocytosis and IL-1β production.
abstract: Surfactant protein A (SP-A), a pulmonary collectin, plays a role in lung innate immune host defense. In this study the role of SP-A in regulating the inflammatory response to the flagella of Pseudomonas aeruginosa (PA) was examined. Intra-tracheal infection of SP-A deficient (SP-A-/-) C57BL/6 mice with wild type flagellated PA (PAK) resulted in an increase in inflammatory cell recruitment and increase in pro-inflammatory cytokines IL-6 and TNF-α, which was not observed with a mutant pseudomonas lacking flagella (fliC). SP-A directly bound flagellin, via the N-linked carbohydrate moieties and collagen-like domain, in a concentration dependent manner and enhanced macrophage phagocytosis of flagellin and wild type PAK. IL-1β was reduced in the lungs of SP-A-/- mice following PAK infection. MH-s cells, a macrophage cell line, generated greater IL-1β when stimulated with flagellin and SP-A. Historically flagella stimulate IL-1β production through the toll-like receptor 5 (TLR-5) pathway and through a caspase-1 activating inflammasome pathway. IL-1β expression became non-detectable in SP-A and flagellin stimulated MH-s cells in which caspase-1 was silenced, suggesting SP-A induction of IL-1β appears to be occurring through the inflammasome pathway. SP-A plays an important role in the pathogenesis of PA infection in the lung by binding flagellin, enhancing its phagocytosis and modifying the macrophage inflammatory response.
authors: Department of Pediatrics, Division of Neonatology, Division of Pediatric Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Anastasia K
authors: AK
authors: Ketko
authors: Chinhong
authors: C
authors: Lin
authors: Bethany B
authors: BB
authors: Moore
authors: Ann Marie
authors: AM
authors: LeVine
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005408:Flagellin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D010587:Phagocytosis / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D037662:Pulmonary Surfactant-Associated Protein A; D005408:Flagellin