Surfactant Protein-D Regulates Surfactant Phospholipid Homeostasis in Vivo

TLDR

Surfactant protein D is a 43‑kDa collectin expressed in lung epithelial cells that participates in pulmonary innate immunity. The SP‑D gene was disrupted by homologous recombination in embryonic stem cells, generating heterozygous and knockout mice. Loss of SP‑D caused marked increases in alveolar phosphatidylcholine, foamy macrophages, enlarged alveoli, abnormal surfactant structure, and reduced SP‑A, revealing a previously unsuspected role for SP‑D in surfactant lipid homeostasis.

Abstract

Surfactant protein D (SP-D) is a 43-kDa member of the collectin family of collagenous lectin domain-containing proteins that is expressed in epithelial cells of the lung. The SP-D gene was targeted by homologous recombination in embryonic stem cells that were used to produce SP-D (±) and SP-D (−/−) mice. Both SP-D (−/−) and SP-D (±) mice survived normally in the perinatal and postnatal periods. Whereas no abnormalities were observed in SP-D (±) mice, alveolar and tissue phosphatidylcholine pool sizes were markedly increased in SP-D (−/−) mice. Increased numbers of large foamy alveolar macrophages and enlarged alveoli were also observed in SP-D (−/−) mice. Phospholipid composition was unaltered in SP-D (−/−) mice, but surfactant morphology was abnormal, consisting of dense phospholipid membranous arrays with decreased tubular myelin. The pulmonary lipoidosis in the SP-D (−/−) mice was not associated with accumulation of surfactant proteins B or C, or their mRNAs, distinguishing the disorder from alveolar proteinosis syndromes. Surfactant protein A mRNA was reduced and, SP-A protein appeared to be reduced in SP-D (−/−) compared with wild type mice. Targeting of the mouse SP-D gene caused accumulation of surfactant lipid and altered phospholipid structures, demonstrating a previously unsuspected role for SP-D in surfactant lipid homeostasis <i>in vivo</i>.