Chronic obstructive pulmonary disease (COPD) is one of the most common inflammatory diseases resulting from habitual smoking. Impaired clearance of apoptotic cell by airway macrophages contributes to lung inflammation. Milk fat globule-EGF factor 8 (MFG-E8), as a link between apoptotic cells and phagocytes, facilitates clearance of apoptotic cells and attenuates inflammation. We sought to investigate altered expression and potential role of MFG-E8 in COPD. In this study, apoptosis was increased and the level of MFG-E8 was decreased while HMGB1 expression was increased in lung tissues of CS-exposed mice. Compared with CS-exposed WT mice, more apoptotic cells were accumulated in lung tissues of CS-exposed MFG-E8 deficiency mice. Exposure of a range of macrophages to cigarette smoke extract (CSE) resulted in decreased MFG-E8 expression. Administration of rmMFG-E8 ameliorated phagocytic ability of RAW264.7 cells and suppressed inflammatory response induced by CS-exposure. 10% CSE stimulation suppressed Rac1 membrane localization in RAW264.7 cells which was restored by administration of rmMFG-E8. MFG-E8 deficiency diminished uptake of apoptotic thymocytes by peritoneal macrophages upon CSE exposure. Overall, the findings in current work provide a novel target for diagnosing and treating COPD.

We have developed a novel egg yolk antibody (IgY)–coated magnetic beads antigen-capture immunoassay for detection of a circulating antigen of Schistosoma japonicum in serum samples of patients in schistosomiasis-endemic areas of China. This IgY-based immunomagnetic bead enzyme-linked immunosorbent assay (IgY-IMB-ELISA) uses polyclonal IgY-coated magnetic beads as a capture antibody, and a monoclonal IgG as a detection antibody. The sensitivity of the magnetic immunoassay was 100% (40 of 40) in cases of acute infection and 91.5% (107 of 117) in chronic cases of schistosomiasis, and no positive reaction was found in 0 of 49 healthy persons. Cross-reactivity was 3.3% (1 of 33) with clonorchiasis and 0% (0 of 20) with paragonimiasis. There was a significant correlation between ELISA absorbance value and egg count (eggs per gram feces) and a correlation coefficient of 0.88 in a small sample of 14 patients. The results demonstrated that the IgY-IMB-ELISA is a sensitive and specific assay for detection of human schistosomiasis japonica.

Milk fat globule epidermal growth factor 8 (MFG-E8) is an opsonin involved in the phagocytosis of apoptotic cells. In patients with chronic obstructive pulmonary disease (COPD), apoptotic cell clearance is defective. However, whether aberrant MFG-E8 expression is involved in this defect is unknown. In this study, we examined the expression of MFG-E8 in COPD patients. MFG-E8, interleukin (IL)-1β and transforming growth factor (TGF)-β levels were measured in the plasma of 96 COPD patients (93 males, 3 females; age range: 62.12±10.39) and 87 age-matched healthy controls (85 males, 2 females; age range: 64.81±10.11 years) using an enzyme-linked immunosorbent assay. Compared with controls, COPD patients had a significantly lower plasma MFG-E8 levels (P<0.01) and significantly higher plasma TGF-β levels (P=0.002), whereas there was no difference in plasma IL-1β levels between the two groups. Moreover, plasma MFG-E8 levels decreased progressively between Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and GOLD IV stage COPD. Multiple regression analysis showed that the forced expiratory volume in 1 s (FEV1 % predicted) and smoking habit were powerful predictors of MFG-E8 in COPD (P<0.01 and P=0.026, respectively). MFG-E8 was positively associated with the FEV1 % predicted and negatively associated with smoking habit. The area under the receiver operating characteristic curve was 0.874 (95% confidence interval: 0.798-0.95; P<0.01). Our findings demonstrated the utility of MFG-E8 as a marker of disease severity in COPD and that cigarette smoke impaired MFG-E8 expression in these patients.

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