Eicosapentaenoic acid inhibits antigen-presenting cell function of murine splenocytes.

Recently, many investigators have studied the effects of eicosapentaenoic acid (EPA)-rich fish oil on immune function and immune disease. However, effects of dietary supplementation of fish oil or EPA on the immune system are still unclear. In the present study, the effects of EPA on antigen presentation were investigated. We have used antigen-specific helper T-cell clones that proliferate in the presence of antigen [keyhole limpet haemocyanin (KLH)] and spleen cells as antigen-presenting cells (APC). Mice were divided into two groups and fed an experimental diet or a control diet for 4 weeks ad libitum. In mice fed the experimental diet, the arachidonic acid (AA) content of spleen cells was decreased and that of EPA and docosapentaenoic acid was increased markedly compared to those of the control diet. Dietary enrichment with EPA inhibited the ability of accessory cells to present antigen to murine helper T-cell clones. This effect was observed for two distinct helper T-cell clones, Th1 and Th2. We also examined the effects of EPA-TG emulsion on APC function. The direct addition of EPA-TG emulsion to a T-cell proliferation assay system suppressed APC function. The inhibition was proportional to the concentration of EPA-TG emulsion. Pretreatment of splenocytes with EPA-TG emulsion resulted in inhibition of APC function. Inhibition of antigen presentation by dietary supplementation with EPA might depress immune reactivity.     

The expression of human leukocyte antigen-G on trophoblasts abolishes the growth-suppressing effect of interleukin-2 towards them

PROBLEM: We have shown the attenuated human leukocyte antigen (HLA)-G expression on trophoblasts and an aberrant expression of interleukin (IL)-2, a cytotoxic cytokine, in decidual tissue in preeclampsia, where deteriorated trophoblastic invasion into decidual layers may constitute a crucial pathogenesis. We hypothesized that the absence of HLA-G might make trophoblasts susceptible to compromise by IL-2. METHOD OF STUDY: We analyzed the growth of HLA-G-negative and positive cell lines, all of which possessed IL-2 receptors, in the culture with or without IL-2 supplementation. RESULTS: The proliferation of HLA-G positive trophoblastic cell lines (BeWo and JEG-3) was not influenced by the addition of IL-2, whereas a HLA-G-negative trophoblastic cell line (JAR) exhibited significantly decreased proliferation when cultured with IL-2. Interestingly, the transfection of JAR cells with HLA-G completely eliminates the growth-inhibitory effect of IL-2. CONCLUSION: The expression of HLA-G may commit trophoblasts to evade cell damage by IL-2, which may be relevant to maternal tolerance of the fetus during pregnancy and its derangement as exemplified by preeclampsia.     

Regional differences of PCB and PCQ concentrations in the blood and subcutaneous fat tissue of residents of Nagasaki

In this study, we analyzed PCB and PCQ concentrations in the subcutaneous fat tissue of residents of Nagasaki Prefecture, and compared these levels between the blood and subcutaneous fat tissue of people living in various parts of the prefecture. Seventy-one inhabitants were examined. In the blood, PCB concentrations in Tamanoura and Fukue were significantly higher than those in Nagasaki City. The CB% ratio in Tamanoura was significantly higher than that in Nagasaki and Isahaya. PCQ concentrations were below detection level except in one case. PCB concentrations in fishery areas showed higher levels than urban or agricultural areas. PCB concentration in the subcutaneous fat tissue was 100 times higher than that in the blood. PCQs could be detected in almost all of the subcutaneous tissues, but there was no regional difference in the PCQ concentration.     

Foamy cells in itp spleens and in granulomas induced by murine platelets, commercialized phospholipids, and erythrocyte membrane. Histological and ultrastructural studies

A large number of foamy cells were noted in the spleens from fourteen ITP patients, and two patients who received a large amount of platelet rich plasma. Using the unlabelled immunoperoxidase method, these foamy cells were shown to contain platelet antigen. Platelets in varying stages of intracellular digestion, from intact-appearing forms to myelin-like materials, were disclosed in foamy cells. Foamy cells were experimentally induced in granulomas by subcutaneous injection of platelets with or without accompanied administration of steroid, the platelets reacted with anti-murine platelet antibody, commercialized phospholipids (PE, PC, SM, PS, and the mixture of them), and the red blood cell membrane. The foamy cells induced by the subcutaneous injection of platelets are similar to those in the spleens of ITP patients. The lipid in foamy cells is chiefly derived from the membrane phospholipid of injected platelets. Concentric myelin-like materials were also noted in the foamy cells after injection of erythrocyte membrane. The myelin-like materials in these foamy cells are similar to those appearing in macrophages following injection of PC and SM. This suggests that these phospholipids derived from cell membrane are more resistant to intracellular digestion by lysosomal enzymes. We conclude that the foamy appearance of the cordal macrophage in ITP spleens results from incomplete intracellular degradation of platelet membrane.     

Thymocyte activating factors from SV40-transformed human embryo fibroblasts

A novel factor was found in the medium conditioned by SV40-transformed human embryo fibroblasts, which stimulate concanavalin A-induced thymocyte DNA synthetic response. This activity was estimated to be 10-15 kD and divided into two activities by ion exchange chromatography. One of them is a protein molecule and the other is a glycoprotein. In addition, these activities are not derived from the growth factors reported previously such as interleukin 2 (Morgan, R., Ruscetti, F. and Gallo, R. C. (1976) Science 193, 1007-1008) and transforming growth factor (De Larco, J. E. and Todaro, G. J. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 4001-4005).     

Endocytosis of human thyroglobulin (TG) in adenomatous goiter studied by an immuno-electron microscopic procedure

Five cases of adenomatous goiter have been studied by an electron microscope using an immuno-reaction for thyroglobulin (TG) and focusing on the mechanism of endocytosis. Positive stain for TG was demonstrated in follicular lumina, large reabsorbed colloid droplets and small subapical vesicles. Endocytotic vesicles ranging from 320 nm to 1600 nm in diameter were observed in the cytoplasm as pits in the apical plasma membrane. Some of them showed direct connection with the positive stain for TG in the follicular lumen and the others were completely ingested in the cytoplasm. With statistic analysis, a majority of the vesicles showing the positive stain for TG in the cytoplasm distributed in the range of 200 nm to 1200 nm in diameter with the peak in 300 nm to 399 nm and was situated within an extent of the diameter measured from the endocytotic vesicles. Engulfment of colloid by pseudopods and fusion of the reabsorbed colloid droplets were encountered as extremely rare findings and appeared to play no major role for formation of large colloid droplets in adenomatous goiter.     

Phasically firing neurons in the supraoptic nucleus of the rat hypothalamus: immunocytochemical and electrophysiological studies

Relations between firing patterns and peptides in supraoptic neurons of rat hypothalamic slice preparations were studied by electrophysiology, intracellular fluorescent dye-marking and immunocytochemistry. Seven out of 10 magnocellular neurons which showed phasically firing patterns were identified by injections of Lucifer Yellow-CH (LY); these were also stained with an anti-vasopressin serum. This report presents direct evidence that most of the phasically firing neurosecretory neurons in the supraoptic nucleus contain vasopressin. This study demonstrates the feasibility of combining immunocytochemical and electrophysiological techniques to study the peptides contents of single mammalian neurons.     

Familial amyloidotic polyneuropathy (ATTR Ser50Ile): the first autopsy case report

We report an autopsy case of a pedigree of familial amyloidotic polyneuropathy (FAP) with a mutation of isoleucine-50 transthyretin (ATTR Ser50Ile). A 47-year-old man started developing severe diarrhea and weight loss at age 41 years, followed by urinary incontinence, autonomic-nervous-system abnormalities and serious heart failure; the diagnosis of FAP (ATTR Ser50Ile) was made on the basis of genetic, histochemical and immunohistochemical analysis. Six years after the initial symptoms, he died of septic shock. Autopsy revealed suppurative peritonitis, perforation of the sigmoid colon and marked systemic amyloid deposition. The total amount of amyloid deposited in the heart was greatly increased and was much lower in the thyroid gland and kidneys compared with amyloid deposits in ordinary FAP (ATTR Val30Met). Amyloid deposition in peripheral vessel walls was prominent, particularly in lymphatics and veins. His elder sister, 54 years old, started to develop orthostatic hypotension at age 49 years, followed by dysesthesia, diarrhea and severe congestive heart failure. Endomyocardial biopsy revealed severe TTR–amyloid deposition; ultrastructural examination demonstrated that amyloid fibrils were deposited disproportionately and extended radially around microvessels. These characteristic patterns of systemic amyloid deposition and distinct clinical manifestations, especially in the cardiovascular system, are considered to be a characteristic feature of ATTR Ser50Ile amyloidosis. Received: 31 August 1999 / Accepted: 19 October 1999     

Antibody masking renders HIV-1 resistant to cationic membrane filtration through alteration of its electrostatic characteristics

Previously, it was demonstrated that any human immunodeficiency virus type 1 (HIV-1) strain proliferating in peripheral blood mononuclear cells (PBMCs) in vitro, and resuspended in seronegative plasma, could be captured efficiently (mean > 95%) by a porous polypropylene (PP) membrane modified cationically. We investigated if this cationic membrane could capture HIV-1 obtained from seropositive plasma, and confirmed whether this membrane was effective for the preparation of safe plasma products against HIV-1 transmission. Thirty-six seropositive plasma samples derived from HIV-1 positive cohorts in New York and Lusaka (Republic of Zambia), including 18 cases of acquired immunodeficiency syndrome (AIDS) related complex, AIDS and five terminal cases of AIDS, were filtered through the cationic membrane to determine the reduction of RNA concentration, the gag p24 concentration, and infectious titer. Only a small reduction in RNA concentration (mean < 20%) and almost no decrease in gag concentration (mean < 2%) were obtained, despite the fact that the infectivity was eliminated entirely by the filtration. Due to the possibility that anti-HIV-1 antibodies in patients' plasma combine with HIV-1, laboratory-adapted HIV-1(HTLV-IIIB) was mixed with seropositive plasma to test the effect of antibodies on HIV-1 adsorption, and also to investigate the interfacial electrokinetic potential (zeta-potential) of both intact and plasma-treated HIV-1. The zeta-potential of HIV-1(HTLV-IIIB) in the presence of seropositive plasma was neutral as opposed to negative when stored in seronegative plasma or culture medium. Also the rate of HIV-1 capture by the membrane, as determined by the reduction in RNA concentration, sank from 95% to 20%, the same capture percentage observed when filtering plasma of patients. These findings suggested that in patients' plasma, the antibody-masked HIV-1 comprise most of the viral population, and was not trapped on the cationic membrane because of its electrostatic character. Conversely, the cationic membrane was thought to adsorb antibody-free HIV-1 exclusively. It was suggested that each viral swarm had its own zeta-potential, and this difference in electrostatic character determined the extent of the viral adsorption by the cationic membrane.