Surfactant Protein A Attenuates Generalized and Localized Neuroinflammation In Neonatal Mice

Abstract

Abstract Background: Surfactant protein A (SP-A) has important roles in innate immunity, attenuation of pulmonary inflammation and modulation of extrapulmonary inflammation. SP-A has been detected in rat and human brain, but its function in the central nervous system is untested. Our objective was to determine whether SP-A has a role in modulating inflammation in the neonatal mouse brain. Methods: Neonatal wildtype (WT) and SP-A-deficient (SP-A-/-) C57BL/6J mice were subjected to three models of brain inflammation: sepsis through intraperitoneal injection of lipopolysaccharide (LPS), intraventricular hemorrhage (IVH) through intraventricular injection of hemoglobin and hypoxic-ischemic encephalopathy (HIE) through unilateral carotid artery ligation and hypoxia. Following treatment, RNA was isolated from brain tissue and expression of cytokine (IL-1β, IL-6, CXCL1, TNF-α, and IL-10) mRNA was determined by real-time quantitative RT-PCR analysis. Expression of SP-A mRNA in mouse brain was determined by RT-PCR analysis. Results: In the sepsis model, levels of most cytokine mRNAs were significantly increased in WT and SP-A-/- mouse brain tissue subjected to LPS injection compared to saline control, and all cytokine mRNA levels were significantly greater in SP-A-/- mouse brain tissue compared to WT. In the IVH model, all cytokine mRNAs were significantly increased in WT and SP-A-/- brain tissue subjected to intraventricular hemoglobin injection compared to saline control, and levels of cytokine mRNAs were significantly increased in SP-A-/- mouse brain tissue compared to WT. In the HIE model, only TNF-a mRNA levels were significantly increased in WT brain tissue subjected to carotid artery ligation compared to sham + hypoxia control, but most cytokine mRNAs were significantly increased in SP-A-/- mouse brain tissue and all cytokine mRNA levels were significantly higher in SP-A-/- mouse brain tissue compared to WT. SP-A mRNA was not detectable in brain tissue of adult WT mice nor of WT neonates subjected to the neuroinflammatory models. Conclusions: In neonatal mice subjected to models of neuroinflammation, cytokine mRNA expression was significantly greater in SP-A-/- brain tissue compared to WT. These results suggest that SP-A-/- mice are more susceptible to generalized and localized neuroinflammation than WT mice, thus supporting the hypothesis that SP-A attenuates inflammation in the neonatal mouse brain.