Lerdelimumab

Natural cell membranes derived from various cell sources have been successfully utilized to coat nanomaterials for functionalization. However, intracellular membranes from the organelles of eukaryotes remain unexplored. Herein, we choose mitochondrion as a representative cell organelle and coat outer mitochondrial membrane (OMM) from mouse livers onto nanoparticles and field-effect transistors (FETs) through a membrane vesicle-substrate fusion process. Polymeric nanoparticles coated with OMM (OMM-NPs) can bind with ABT-263, a B-cell lymphoma protein 2 (Bcl-2) inhibitor that targets the OMM. As a result, OMM-NPs effectively protect the cells from ABT-263 induced cell death and apoptosis in vitro and attenuated ABT-263-induced thrombocytopenia in vivo. Meanwhile, FET sensors coated with OMM (OMM-FETs) can detect and distinguish anti-Bcl-2 antibody and small molecule agonists. Overall, these results show that OMM can be coated onto the surfaces of both nanoparticles and functional devices, suggesting that intracellular membranes can be used as coating materials for novel biointerfacing.

Cardiac asthma describes symptoms of airflow obstruction due to heart failure. Chronic heart failure is associated with decreased FEV 1 , and FEV 1 improves after heart transplantation. Fibrotic remodeling of the heart and airways is mediated, in part, through transforming growth factor (TGF)- β . Blood TGF- b 1 concentration correlates with ventricular remodeling in cardiac disease, and TGF- β decreases after repair.

We established a coculture of normal human bronchial epithelial (NHBE) cells differentiated at air-liquid interface with submerged basal cardiomyoblasts. Airway cells were immunostained with cytokeratin, actin, and involucrin. TGF- β synthesis was assayed using enzyme-linked immunosorbent assay. Phosphorylation of Smad in NHBE cells was determined by Western blotting.Mice given doxorubicin developed cardiac failure, and their airways were histologically examined.

Coculture induced involucrin-positive squamous metaplasia of NHBE cells, and this was attenuated by TGF- β antibody. Total TGF- β 1 was increased in coculture conditioned medium( P < .001). After 14 days of exposure to recombinant TGF- β 1 , there was squamous transformation of NHBE cells. One week after removing cardiomyoblasts from culture, squamous metaplasia resolved into normal ciliated epithelia. Smad was phosphorylated in NHBE cells with cardiomyoblasts or with recombinant TGF- β 1 exposure. The airways of mice with heart failure also demonstrated involucrin-positive squamous transformation.

TGF- β from cardiomyoblasts or from the failing heart can cause airway squamous metaplasia via Smad signaling, and this is blocked by anti-TGF- b antibody and reversed when cardiac cells are removed from culture. This appears to be an important mechanism for airflow obstruction with heart failure, sometimes described as cardiac asthma.