title: Pulmonary surfactant protein A protects lung epithelium from cytotoxicity of human β-defensin 3.
abstract: Defensins are important molecules in the innate immune system that eliminate infectious microbes. They also exhibit cytotoxicity against host cells in higher concentrations. The mechanisms by which hosts protect their own cells from cytotoxicity of defensins have been poorly understood. We found that the cytotoxicity of human β-defensin 3 (hBD3) against lung epithelial cells was dose-dependently attenuated by pulmonary surfactant protein A (SP-A), a collectin implicated in host defense and regulation of inflammatory responses in the lung. The direct interaction between SP-A and hBD3 may be an important factor in decreasing this cytotoxicity because preincubation of epithelial cells with SP-A did not affect the cytotoxicity. Consistent with in vitro analysis, intratracheal administration of hBD3 to SP-A(-/-) mice resulted in more severe tissue damage compared with that in WT mice. These data indicate that SP-A protects lung epithelium from tissue injury caused by hBD3. Furthermore, we found that the functional region of SP-A lies within Tyr(161)-Lys(201). Synthetic peptide corresponding to this region, tentatively called SP-A Y161-G200, also inhibited cytotoxicity of hBD3 in a dose-dependent manner. The SP-A Y161-G200 is a candidate as a therapeutic reagent that prevents tissue injury during inflammation.
authors.affiliation: Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ariki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sohma
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nishitani
authors.forename: Kanako
authors.initials: K
authors.lastname: Inoue
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ebata
authors.forename: Motoko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Koji
authors.initials: K
authors.lastname: Kuronuma
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kuroki
mesh_terms: D000818:Animals; D002460:Cell Line; D003603:Cytotoxins / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000494:pharmacology*; D011014:Pneumonia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D023083:beta-Defensins / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D003603:Cytotoxins; D010455:Peptides; D037662:Pulmonary Surfactant-Associated Protein A; D023083:beta-Defensins