Haruyuki Shirasawa

Fc receptors of liver sinusoidal endothelium in normal rats and humans: A histologic study with soluble immune complexes

Fc receptors for immunoglobulin G in the liver sinusoidal wall were studied in the normal rat and in humans by applying peroxidase-antiperoxidase immunoglobulin G complexes to the frozen sections. Fc receptors were found to exist continuously along the sinusoidal lining. The receptors showed no zonal distribution in the rat, and they were generally scarce near the central veins and portal areas in humans. To characterize the sinusoidal cells, carbon or latex was given intravenously and endogenous peroxidase was demonstrated for the rat, whereas factor VIII-related antigen and endogenous peroxidase were demonstrated for the humans. In the rat, Fc receptors were detected on Kupffer cells, which were characterized by an intense endogenous peroxidase activity and ingestion of latex or quantities of carbon. They were also detected on sinusoidal endothelial cells, which were characterized by undetectable peroxidase activity and no ingestion of latex nor of a small quantity of carbon. In humans, Fc receptors were also present on Kupffer cells as well as sinusoidal endothelial cells, as identified by endogenous peroxidase and factor VIII-related antigen, respectively.

Identification of two novel amyloid A protein subsets coexisting in an individual patient of AA-amyloidosis

Amyloid A protein (AA), the major fibril protein in AA-amyloidosis, is an N-terminal cleavage product of the precursor protein, serum amyloid A (SAA). Using mass spectrometry and amino-acid sequencing, we identified and characterized two novel AA protein subsets co-deposited as amyloid fibrils in an patient having AA-amyloidosis associated with rheumatoid arthritis. One of the AA proteins corresponded to positions 2-76 (or 75) of SAA2 alpha and the other corresponded to positions 2-76 (or 75) of known SAA1 subsets, except for position 52 or 57, where SAA1 alpha has valine and alanine and SAA1 beta has alanine and valine in position 52 and 57, respectively, whereas the AA protein had alanine at the both positions. Our findings (1), demonstrate that not only one but two SAA subsets could be deposited together as an AA-amyloid in a single individual and (2), support the existence of a novel SAA1 allotype, i.e., SAA152,57Ala.

Alveolar soft part sarcoma of the tongue Report of a case

The clinicopathologic, immunohistological, and ultrastructural features of an alveolar soft part sarcoma of the tongue occurring in a 2-year-old girl are described. A primary alveolar soft part sarcoma arising in the dorsum part of the tongue is quite rare. There has been no recurrence or metastasis as of 7 years postoperatively.

Intrasellar neuronal choristoma associated with growth hormone-producing pituitary adenoma containing amyloid deposits

The histological, immunocytochemical, and ultrastructural features of an intrasellar neuronal choristoma associated with pituitary growth hormone (GH)-producing adenoma are reported. Immunohistochemistry studies and electron microscopy examination showed the adenoma cells to be positive for GH but negative for prolactin, and the neurons of the choristoma to have GH-releasing factor (GRF) neurosecretory activity. The adenoma also had many amyloid deposits in its extracellular space immunoreactive to GRF. This is the first report of the tumor containing amyloid deposits.

C1q production and C1q-mediated immune complex retention in lymphoid follicles of rat spleen

SummaryInvolvement of C1q in retaining immune complexes in germinal centers in rat spleen was studied in vivo and in vitro. C1q production was found in fibroblastic reticulum cells in the peripheral mantle zone, in follicular dendritic cells in germinal centers, and in transitional forms between these two cells in the inner mantle zone. In passively immunized animals, immune complexes were found transiently on fibroblastic reticulum cells, then on the transitional forms and follicular dendritic cells. Extracellular C1q was detected by the presence of immune complexes on both the transitional forms and follicular dendritic cells, but not on fibroblastic reticulum cells. Thus, the fibroblastic reticulum cell appeared to trap immune complexes but not to retain either immune complexes or C1q. The morphology and function of the fibroblastic reticulum cell and the follicular dendritic cell suggest that they belong to the same lineage. Immune complexes were bound in vitro to germinal centers in cryostat spleen sections in the same manner as those retained in vivo. The binding required no complement in the incubation medium and was inhibited by C1q-suppressing factors. The extracellular C1q originating from the follicular cells may therefore play a role in retaining immune complexes in the germinal center.

Osteochondroma of the mandibular condyle. Report of a case and review of the Japanese literature.

A case of osteochondroma of the mandibular condyle causing severe facial asymmetry and malocclusion (occlusal deviation) is presented. A 63-year-old woman was successfully treated by removal of the tumor and condylectomy. In addition, 4 cases of osteochondroma of the mandibular condyle reported in the Japanese literature are reviewed with respect to several clinical items.

Defect of sinusoidal Fc receptors and immune complex uptake in CCl4-induced liver cirrhosis in rats.

The purpose of this paper is to provide a histopathologic basis for abnormalities in immune-complex clearance in liver disease. Fc receptors in CCl4-induced liver cirrhosis in rats were studied by applying peroxidase-antiperoxidase immunoglobulin G complex as a ligand to the frozen sections. Intravenous injection of bovine serum albumin-antibovine serum albumin complexes or colloidal carbon was combined with histological staining for endogenous peroxidase, fibronectin, laminin, or a lectin, Bandeiraea simplicifolia agglutinin I. In the cirrhotic process, sinusoidal Fc receptors showed a weakened reactivity to the ligand with focal absence, and the length of the Fc receptor-positive portion of the sinusoids in unit area decreased to about 50% of the normal value in the advanced cirrhosis. Fibronectin and the lectin showed the presence of sinusoids where Fc receptors were absent. The endothelium in Fc receptor-negative areas did not take up either immune complexes or carbon, and Kupffer cells were absent in these areas. A disturbed immune-complex metabolism was thus suggested to occur in association with the defect of sinusoidal Fc receptors in liver cirrhosis. These abnormalities appeared to not be directly related to perisinusoidal laminin deposition, i.e., capillarization of the sinusoid.

LOCALIZATION OF Fc RECEPTORS ON LIVER SINUSOIDAL ENDOTHELIUM A Histological Study by Electron Microscopy

The localization of Fc receptors for IgG on mouse liver sinusoidal endothelium was studied in tissue sections by light and electron microscopy using peroxidase‐antiperoxidase IgG complexes as ligands. Light microscopy revealed that Fc receptors were continuously present along the sinusoidal wall, but absent on the endothelium of the central vein and that of the portal area blood vessels. Electron microscopy revealed Fc receptors on both the luminal and basal aspects of the plasma membrane, far more being present on the former, on the walls of cytoplasmic fenestrae, and abundantly on the walls of coated pits and vesicles of sinusoidal endothelial cells. Fc receptors were found more frequently on sinusoidal endothelial cells than on Kupffer cells. Fat‐storing cells lacked the receptors and hepatocytes showed an ambiguous result which was considered to be nonspecific.

Intraperitoneal amyloid formation by amyloid enhancing factor--rich macrophages in ascitic fluid.

Although resident peritoneal cells from amyloidotic mice (amyloidotic peritoneal cells) are capable of processing the precursor protein of secondary amyloidosis, serum amyloid A (SAA) to amyloid fibrils, the peritoneum is a rare site for amyloid deposition. This is considered to be due to a deficiency of SAA in the peritoneum. To increase the supply of SAA to the peritoneum, ascitic fluid containing about the same protein constituents as in the serum was induced in mice. Amyloidotic peritoneal cells were packed in a microchamber which was shielded with filter membranes, and cultured in ascitic fluid supplemented with additional inflammatory factors. On the 7th day, Congo red-positive structures which showed green birefringence under polarized light were found inside and occasionally outside the chamber. By anti-AA or -SAA immunostaining, amyloid deposits and the cell surfaces of macrophages were positive. Immunologic depletion of T- and B-lymphocytes from the amyloidotic peritoneal cells did not adversely effect the amyloid formation in microchambers. These results suggest that either ascitic fluid containing sufficient amounts of SAA, or peritoneal macrophages with a high amyloid enhancing factor (AEF) activity are indispensable for AA amyloid fibrillogenesis in the peritoneum.

Alterations in Fc receptor activity in sinusoidal endothelial cells and Kupffer cells during D-galactosamine (GalN)-induced liver injury in rats

SummaryFc receptors in sinusoidal cells and immune complex uptake were studied histologically in D-galactosamine HC1 (GalN)-induced liver injury in rats. Kupffer cells and monocytes were distinguished from sinusoidal endothelial cells and from each other by endogenous peroxidase staining. Fc receptors were found along the sinusoidal endothelium throughout the lobules in normal livers. In acute injury caused by 300 or 750 mg/kg of GalN, Fc receptors were preserved within necrotic foci until the foci were infiltrated by inflammatory cells. The endothelial Fc receptor activity altered, as demonstrated by their capacity to bind immune complexes, after GalN injection. The activity decreased from 24 h after injection in the periportal areas in both dose groups, and increased transiently with dose-dependence in the remaining areas. Kupffer cell numbers also showed a transient dose-dependent increase, except in the periphery of lobules where they generally decreased. In chronic injury with 400 mg/kg, Fc receptors were lost and Kupffer cells decreased in the periportal areas. Circulating immune complexes were ingested by Kupffer cells and endothelial cells in normal and injured livers, showing the the same distribution as that of Fc receptors except that the complexes decreased gradually towards the centrilobular zones.