The spike (S) protein of coronavirus, which binds to cellular receptors and mediates membrane fusion for cell entry, is a candidate vaccine target for blocking coronavirus infection. However, some animal studies have suggested that inadequate immunization against severe acute respiratory syndrome coronavirus (SARS-CoV) induces a lung eosinophilic immunopathology upon infection. The present study evaluated two kinds of vaccine adjuvants for use with recombinant S protein: gold nanoparticles (AuNPs), which are expected to function as both an antigen carrier and an adjuvant in immunization; and Tolllike receptor (TLR) agonists, which have previously been shown to be an effective adjuvant in an ultraviolet-inactivated SARS-CoV vaccine. All the mice immunized with more than 0.5 µg S protein without adjuvant escaped from SARS after infection with mouse-adapted SARS-CoV; however, eosinophilic infiltrations were observed in the lungs of almost all the immunized mice. The
Epidermal growth factor (2 -50 nglml), prepared from mouse submaxillary glands, stimulated growth and the synthesis of non-collagenous proteins and hyaluronic acid, but inhibited collagen synthesis in cultured human skin fibroblasts, both stimulation and inhibition being dose-dependent. All these effects may be intrinsic functions of the epidermal growth factor molecule, because these effects were cancelled by the co-presence of antiserum specific for epidermal growth factor and because they were also observed following the addition of human epidermal growth factor produced urogastrone cDNA. On the other hand, L-ascorbate (vitamin C) stimulated growth and collagen synthesis, as well as synthesis of non-collagenous proteins, with no significant effect on hyaluronic acid synthesis.Co-presence of epidermal growth factor and ascorbate gave additive effects on growth and protein synthesis of the cells. These results suggest that the two growth-promoting factors, epidermal growth factor and L-ascorbate, modulate metabolism of extracellular matrix components as well as cell growth in a quite different manner in human skin fibroblasts.Epidermal growth factor (EGF), first isolated from male mouse submaxillary glands, is a 53-amino-acid polypeptide [l]. It modulates the growth properties of many types of cells including cells of mesenchymal origin such as fibroblasts [2] and osteoblasts [3, 41 in addition to cells of epithelial origin [l]. EGF also regulates a variety of cellular functions including metabolism of extracellular matrix components [4 -71. Urogastrone, isolated from human urine, was noticed by its inhibition of gastric acid secretion and was found to correspond to human EGF (h-EGF) [8, 91.L-Ascorbate (vitamin C), which was first found by its antiscorbutic activity, also has been shown to have multifarious functions on various kinds of cells [lo, 111. One of the most important functions of ascorbate may be its activity as a cofactor for the hydroxylation of proline and lysine residues in collagen [12], which is the most abundant protein present in the animal body. It is also reported that ascorbate increases messenger RNA levels for collagen in cultured fibroblasts [13]. In the course of an investigation on regulatory mechanisms involved in the metabolism of extracellular matrix compoCorrespondence to R. Hata,
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