Yoshiaki Yae

Cloning and Characterization of the Hakata Antigen, a Member of the Ficolin/Opsonin p35 Lectin Family

The Hakata antigen is a novel, thermolabile β2-macroglycoprotein that reacts with sera from patients suffering from systemic lupus erythematosus. In this study we present the structure and the function of the Hakata antigen. We have identified cDNA clones encoding the Hakata antigen and analyzed its function. The cDNA included a possible open reading frame of 897 nucleotides, encoding 299 amino acids. The Hakata antigen consisted of a collagen-like domain in the middle section and a fibrinogen-like domain in the COOH terminus, both of which are homologous to human ficolin-1 and opsonin P35, indicating that these three molecules form a distinct family. The molecular mass of the Hakata antigen expressed in transfected cells was 35 kDa under reduced conditions, and it formed ladder bands under nonreducing conditions compatible with the previous result that the Hakata antigen exists in serum as homopolymers. Purified Hakata antigen sustained lectin activity, showing affinity with GalNAc, GlcNAc, d-fucose as mono/oligosaccharide, and lipopolysaccharides from Salmonella typhimurium andSalmonella minnesota. These results suggest that the Hakata antigen, a new member of the ficolin/opsonin P35 family, plays a role in the serum exerting lectin activity under physiological conditions.

Hakata Antigen, a New Member of the Ficolin/Opsonin p35 Family, Is a Novel Human Lectin Secreted into Bronchus/Alveolus and Bile

Hakata antigen was first reported as a serum protein that reacted with an autoantibody from patients with systemic lupus erythematosus. Recently, it has been found that Hakata antigen is a new member of the ficolin/opsonin p35 family, which is a distinct lectin family, on the basis of homology of structures and the common characteristic of possessing lectin activity. In this study we analyzed the tissue distribution of Hakata antigen. Hakata antigen mRNA and protein were generated in the lung and liver. In the lung, Hakata antigen was produced by both ciliated bronchial epithelial cells and Type II alveolar epithelial cells and was secreted into the bronchus and alveolus. In the liver, Hakata antigen was produced by bile duct epithelial cells and hepatocytes and was also secreted into the bile duct. These results demonstrate that Hakata antigen is a unique lectin protein that exists not only in serum but also in bronchus/alveolus and bile, and indicate that Hakata antigen plays a role in bronchus/alveolus and bile under physiological conditions.

Hypertension-induced cerebral atherosclerosis in the cholesterol-fed rabbit

Foam cell lesions were found in cholesterol-fed rabbits with induced hypertension, particularly in intimal cushions at branching sites, where permeability to horseradish peroxidase was enhanced. Permeability to horseradish peroxidase was enhanced at the edge of intimal cushions without foam cell accumulation. This finding suggests that permeability is increased before foam cell infiltration. No foam cell lesions were observed in the intima of cerebral arteries distant from branching sites, but insudation of plasma constituents here caused endothelial cells to separate from the subendothelial matrices. Foam cell lesions were absent from the cerebral arteries in normotensive cholesterol-fed rabbits.

Effects of hypertension and hypercholesteremia on the permeability of fibrinogen and low density lipoprotein in the coronary artery of rabbits: Immunoelectron-microscopic study

In an attempt to elucidate the effects of hypertension and/or hypercholesteremia on atherogenesis, with special reference to permeation and deposition of fibrinogen and low density lipoprotein (LDL) in the coronary artery, we studied electron-microscopically the localization of fibrinogen and LDL. In the untreated control rabbits, fibrinogen was localized in the caveolae and vesicles of the endothelial cells and in very small amounts in the subendothelial spaces of the coronary artery. Hypertension or hypercholesteremia was related to an enhanced insudation of fibrinogen into the subendothelial spaces of the coronary artery. The insudation of fibrinogen seemed to have occurred by way of vesicular transport and, to some extent, by junctional transport. LDL was localized only in the caveolae and vesicles of the endothelial cells of the coronary artery in the untreated control rabbits. LDL was deposited in the subendothelial space of the hypercholesteremic rabbits, with or without hypertension. Despite the lack of clear-cut and direct evidence, the insudation of LDL into the intima appeared to be enhanced by way of vesicular transport.