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Surfactant protein D (SP-D) is an important innate immune defense molecule that mediates clearance of pathogens and modulates the inflammatory response. Moreover, SP-D is involved in lipid homeostasis, and pulmonary accumulation of phospholipids has previously been observed in SP-D-deficient (Spd-/-) mice. Atherogenesis involves both inflammation and lipid deposition, and we investigated the role of SP-D in the development of atherosclerosis. SP-D synthesis was localized to vascular endothelial cells. Atherosclerotic lesion areas were 5.6-fold smaller in the aortic roots in Spd-/- mice compared with wild-type C57BL/6N mice on an atherogenic diet. HDL cholesterol (HDL-C) was significantly elevated in Spd-/- mice. Treatment of Spd-/- mice with a recombinant fragment of human SP-D resulted in decreases of HDL-C (21%) as well as total cholesterol (26%), and LDL cholesterol (28%). Plasma TNF-[alpha] was reduced in Spd-/- mice (45% difference). SP-D was proatherogenic in the mouse model used. The effect is likely to be due to the observed disturbances of plasma lipid metabolism and alteration of the inflammatory process, which underlie the reduced susceptibility to atherosclerosis in Spd-/- mice. atherosclerosis; experimental animals; high-density lipoprotein; tumor necrosis factor-[alpha];

The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate immune system, but SP-D is also present on extrapulmonary epithelial surfaces and in serum, where it has been used as a biomarker for pulmonary disease states. In this study, we investigate the mechanisms defining the constitutional serum level of SP-D and determine the magnitude of the genetic contribution to serum SP-D in the adult population. Recent studies have demonstrated that serum SP-D concentrations in children are genetically determined and that a single nucleotide polymorphism (SNP) located in the N[H.sub.2]-terminal region (Met11Thr) of the mature protein is significantly associated with the serum SP-D levels. A classic twin study was performed on a twin population including 1,476 self-reported healthy adults. The serum SP-D levels increased with male sex, age, and smoking status. The intraclass correlation was significantly higher for monozygotic (MZ) twin pairs than for dizygotic (DZ) twin pairs. Serum SP-D variance was influenced by nonshared environmental effects and additive genetic effects. Multivariate analysis of MZ and DZ covariance matrixes showed significant genetic correlation among serum SP-D and metabolic variables. The Met11Thr variant explained a significant part of the heritability indicating that serum SP-D variance could be decomposed into non-shared environmental effects ([e.sup.2] = 0.19), additive genetic effects ([h.sup.2] = 0.42), and the effect of the Met11Thr variations ([q.sup.2] = 0.39). surfactant protein D polymorphism; serum marker; interaction of gene and environment; innate immunity

Background: Surfactant Protein D (SP‐D) is a pattern recognition molecule belonging to the family of collectins expressed in multiple human organ systems, including the lungs. Previous studies have shown that SP‐D levels in bronchoalveolar lavage samples decrease and serum levels increase in patients suffering from asthma, possibly due to a combination of induced SP‐D synthesis and decreased air–blood barrier integrity. The aims of this study were to investigate whether serum levels of SP‐D and common variants in the SP‐D gene were associated with asthma in adolescents and young adults. Methods: Prospective observational study including 449 adolescents and young adults (age 11–27 years) previously diagnosed with asthma during a 2‐year period from 2003 to 2005 (0–16 years). At follow‐up from 2016 to 2017, 314 healthy controls with no history of asthma were recruited. Serum SP‐D was analyzed on samples obtained at baseline as well as samples obtained at follow‐up. SP‐D genotyping was performed for rs721917, rs2243639, and rs3088308. Results: No differences were found in mean levels of sSP‐D and SFTPD genotype among subjects with current asthma, no current asthma, and controls. Serum SP‐D and SFTPD genotype were not associated with any clinical parameters of asthma. Furthermore, baseline sSP‐D was not associated with asthma at follow‐up. Conclusion: Serum surfactant protein D and common SP‐D gene variants were not associated with asthma in Danish adolescents and young adults with mild to moderate asthma. Serum surfactant protein D did not demonstrate any value as a clinical biomarker of asthma. [ABSTRACT FROM AUTHOR]

Abstract Background Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr/Thr 11 form of SP-D is associated with low serum levels and assembles predominantly as trimers as opposed to the more common multimeric forms of SP-D. Methods Preliminary experiments were done to establish the effects of different monoclonal antibodies against SP-D on ability of SP-D to bind to or neutralize the virus. We then purified natural human trimeric and multimeric forms of SP-D from amniotic fluid and tested ability of these preparations to bind to IAV, to inhibit infectivity and hemagglutination activity of IAV in vitro. Results In initial experiments mAbs directed against different areas on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to natural human SP-D multimers as well as reduced hemagglutination inhibiting activity against several strains of IAV. Natural SP-D trimers also had different interactions with human neutrophil peptide defensins (HNPs) in viral neutralization assays as compared to multimeric SP-D. Conclusion These studies indicate that a common human polymorphic form of SP-D may modulate host defense against IAV and give impetus to clinical studies correlating this genotype with risk for IAV infection in susceptible groups. We also show that mAbs directed against different areas on the carbohydrate recognition domain of SP-D can be useful for dissecting out different functional properties of the protein.

Background: Alcoholic liver disease (ALD) is a public health concern that is the cause of half of all cirrhosis‐related deaths. Early detection of fibrosis, ideally in the precirrhotic stage, is a key strategy for improving ALD outcomes and for preventing progression to cirrhosis. Previous studies identified the blood‐borne marker human microfibrillar‐associated protein 4 (MFAP4) as a biomarker for detection of hepatitis C virus (HCV)‐related fibrosis. Aim: To evaluate the diagnostic accuracy of MFAP4 to detect ALD‐induced fibrosis. Method: We performed a prospective, liver biopsy‐controlled study involving 266 patients with prior or current alcohol overuse. Patients were split into a training and a validation cohort. Results: MFAP4 was present in fibrotic hepatic tissue and serum MFAP4 levels increased with fibrosis grade. The area under the receiver operating characteristic curve (AUROC) for detection of cirrhosis was 0.91 (95% CI 0.85‐0.96) in the training cohort and 0.91 (95% CI 0.79‐1.00) in the validation cohort. For detection of advanced fibrosis, the AUROC was 0.88 (95% CI 0.81‐0.94) in the training cohort and 0.92 (95% CI 0.83‐1.00) in the validation cohort. The diagnostic accuracy did not differ between MFAP4 and the enhanced liver fibrosis (ELF) test or transient elastography (TE) in an intention‐to‐diagnose analysis. MFAP4 did not predict hepatic decompensation in a time‐to‐decompensation analysis in a subgroup of patients with cirrhosis. Conclusion: MFAP4 is a novel biomarker that can detect ALD‐related fibrosis with high accuracy. [ABSTRACT FROM AUTHOR]