Intravenous surfactant protein D inhibits lipopolysaccharide-induced systemic inflammation.

BACKGROUND: Surfactant protein D (SP-D) is an innate host defense protein that clears infectious pathogens from the lung and regulates pulmonary host defense cells. SP-D is also detected in lower concentrations in plasma and many other non-pulmonary tissues. Plasma levels of SP-D increase during infection and other proinflammatory states; however, the source and functions of SP-D in the systemic circulation are largely unknown. We hypothesized that systemic SP-D may clear infectious pathogens and regulate host defense cells in extrapulmonary systems. METHODS: To determine if SP-D inhibited inflammation induced by systemic lipopolysaccharide (LPS), E.coli LPS was administered to mice via tail vein injection with and without SP-D and the inflammatory response was measured. RESULTS: Systemic SP-D has a circulating half-life of 6 h. Systemic IL-6 levels in mice lacking the SP-D gene were similar to wild type mice at baseline but were significantly higher than wild type mice following LPS treatment (38,000 vs 29,900 ng/ml for 20 mg/kg LPS and 100,700 vs 73,700 ng/ml for 40 mg/kg LPS). In addition, treating wild type mice with purified intravenous SP-D inhibited LPS induced secretion of IL-6 and TNFα in a concentration dependent manner. Inhibition of LPS induced inflammation by SP-D correlated with SP-D LPS binding suggesting SP-D mediated inhibition of systemic LPS requires direct SP-D LPS interactions. CONCLUSIONS: Taken together, the above results suggest that circulating SP-D decreases systemic inflammation and raise the possibility that a physiological purpose of increasing systemic SP-D levels during infection is to scavenge systemic infectious pathogens and limit inflammation-induced tissue injury.

Pulmonary maturational arrest and death in a patient with pulmonary interstitial glycogenosis.

We present the clinical presentation and pathological findings from a term infant with atypical neonatal lung disease. A full term Caucasian male presented at birth with signs of respiratory distress. The respiratory condition continued to deteriorate despite maximum intervention and the patient was placed on ECMO for further cardiorespiratory assistance. An open lung biopsy demonstrated findings consistent with severe lung growth abnormality with non-uniform pulmonary interstitial glycogenosis. The patient consequently developed a pulmonary hemorrhage that required discontinuation of ECMO. The patient died shortly after decannulation. Most literature suggests that PIG is one of the few pediatric interstitial lung diseases that has a favorable prognosis with rare mortality in the absence of co-morbidities. However, the current case suggests prognosis may depend more on the underlying diagnosis than on the histological finding of PIG. In addition, this case may provide insight into the pathogenesis and potential modifiers of this idiopathic disorder.

Surfactant protein D deficiency increases lung injury during endotoxemia.

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are major causes of acute respiratory failure with high rates of morbidity and mortality. Although surfactant protein (SP)-D plays a critical role in pulmonary innate immunity and several clinical studies suggest that this protein may be implicated in the pathophysiology of ARDS, little is known regarding the function of SP-D in ARDS. In the present study, we induced indirect lung injury by intraperitoneal injection of LPS and direct lung injury by intratracheal injection of LPS in wild-type and Sftpd(-/-) mice to elucidate the role of SP-D during ALI/ARDS. Results indicate that pulmonary levels of IL-6 and TNF-α were higher in Sftpd(-/-) mice when compared with wild-type mice. However, the magnitude of this difference was 10-fold greater after indirect lung injury compared with direct lung injury. After indirect lung injury, there was a 2-fold increase in the number of pulmonary monocyte/macrophages in the Sftpd(-/-) mice when compared with wild-type mice, whereas pulmonary neutrophils were not increased. After indirect injury, the concentration of granulocyte-macrophage colony stimulating factor (GM-CSF) was approximately 5-fold greater in Sftpd(-/-) mice than wild-type mice. In contrast, after direct injury, the concentration of GM-CSF was 20-fold less in Sftpd(-/-) mice than wild-type mice. Despite increased inflammatory cells and markers of inflammation, survival in Sftpd(-/-) mice after indirect lung injury was paradoxically increased. In conclusion, these results suggest that SP-D inhibits pulmonary inflammation and migration of peripheral monocyte/macrophages into the lung through GM-CSF-dependent pathways during indirect lung injury.