SIGN-R1, a novel C-type lectin expressed by marginal zone macrophages in spleen,mediates uptake of the polysaccharide dextran

The marginal zone macrophages of the spleen are implicated in the clearance of polysaccharides, but underlying mechanisms need to be pinpointed. SIGN-R1 is one of five recently identified mouse genes that are homologous to human DC-SIGN and encode a single, external, C-terminal C-type lectin domain. We find that a polyclonal antibody to a specific SIGN-R1 peptide reacts primarily and strongly with a subset of macrophages in the marginal zone of spleen and lymph node medulla. In both sites, SIGN-R1 exists primarily in an aggregated form, resistant to dissociation into monomers upon boiling in SDS under reducing conditions. Upon transfection into three different cell lines, high-mol.-wt forms bearing SIGN-R1 are expressed, as well as reactivity with ER-TR9, a mAb previously described to react selectively with marginal zone macrophages. SIGN-R1-expressing macrophages preferentially sequester dextrans following i.v. injection. Likewise, when phagocytic cells are enriched from spleen and tested in culture, dextran is selectively endocytosed by a subset of very large SIGN-R1(+) cells representing approximately 5% of total released macrophages. Uptake of FITC-dextran by these macrophages in vivo and in vitro is blocked by ER-TR9 and polyclonal anti-SIGN-R1 antibodies. Following transfection with SIGN-R1, cell lines become competent to endocytose dextrans. The dextran localizes primarily to compartments lacking transferrin receptor and the LAMP-1 CD107a panlysosomal antigen. Therefore, SIGN-R1 mediates the uptake of dextran polysaccharides, and it is predominantly expressed in the macrophages of the splenic marginal zone and lymph node medulla.     

Contribution of BCAP to maintenance of mature B cells through c-Rel

Mice deficient in the B cell adaptor for phosphoinositide 3-kinase (BCAP) have reduced numbers of mature B lymphocytes, which show defects in cell survival and proliferation. We found here that the NF-kappa B (Rel) pathway was impaired in BCAP-deficient mature B cells and that NF-kappa B target genes, indispensable for cell survival and division, were not induced in response to B cell receptor (BCR) stimulation. Among the NF-kappa B (Rel) family, expression of c-Rel was specifically reduced in BCAP-deficient B cells. Retrovirus-mediated reintroduction of c-Rel restored the pool size of immunoglobulin (Ig)M(lo)IgD(hi) mature B cells in the spleen as well as proliferative responses to BCR stimulation. These results indicate BCAP is essential in the maintenance of mature B cells through functional coupling with c-Rel.     

Relationships between oral allergy syndrome and sensitization to pollen antigen, especially to mugwort]

BACKGROUND: In order to know the relationships between mugwort pollinosis and oral allergy syndrome (OAS), an etiological study was performed at Muroran City, where mugwort is the most frequent cause of pollinosis. METHODS: Allergic rhinitis patients positive to serum IgE to birch, mugwort or grass pollen visited to the outpatient-clinic of Otorhinolaryngology of Muroran City General Hospital from 1998 to 2002, were studied by a questionnaire concerning a past-history of OAS. RESULTS: The prevalence of OAS was significantly higher in patients positive to serum IgE antibody specific to birch pollen or mugwort pollen than those negative to each pollen-specific antibody (birch; 54.5 vs 23.5%, p<0.0001, mugwort; 41.0 vs 21.5%, p<0.01). The main causative foods were fruits of rose family in patients with only birch pollen-specific IgE antibody, and were those other than rose family, such as kiwi, melon, orange, celery and onion in those with only mugwort pollen-specific IgE antibody. The patients group with high Lumiward score to mugwort pollen tended to include severe OAS cases. CONCLUSION: A close relationship was suggested between mugwort pollen sensitization and OAS.     

A peculiar immunoglobulin M (IgM) identified in eggs of chum salmon (Oncorhynchus keta).

A protein reacting with antibody against chum salmon serum IgM was found in salmon egg yolk. The protein tentatively named IgM-like protein was partially purified from egg yolk extract by removal of euglobulin from the extract by dialysis against a low ionic strength buffer following DEAE ion-exchange chromatography. The IgM-like protein was antigenically identical with serum IgM, showing a complete fusion of precipitin line of the IgM-like protein with that of serum IgM on double immunodiffusion with antiserum IgM. The molecular weight of intact IgM-like protein was assessed by 3% SDS-PAGE to be 495 kDa, smaller than that of serum IgM (750 kDa). Upon 10% SDS-PAGE with mercaptane and subsequent Western blotting with antiserum IgM, the IgM-like protein separated into three components with molecular weights of 68 kDa, 51.5 kDa, and 23 kDa. The 68 kDa, the most minor component, and the 23 kDa, the smallest molecular weight component, were identified, respectively, as H and L chain in view of their molecular weights identical to those of serum IgM. The 51.5 kDa, the main component, was also identified as H chain, since it reacted with antiserum IgM absorbed with purified L chain. From these results, it was concluded that the IgM-like protein in egg yolk, having a lower molecular weight than that of serum IgM, consists of H chain of smaller molecular weight as well as H and L chain of ordinary molecular weight.     

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.     

Alterations of 3-nitrotyrosine concentration in the cerebrospinal fluid during aging and in patients with Alzheimer's disease

To investigate the significance of nitric oxide (NO)-mediated neuron death in aging and Alzheimer's disease (AD), the 3-nitrotyrosine concentration in the cerebrospinal fluid (CSF) was investigated in neurologically normal controls and patients with AD. The 3-nitrotyrosine concentration and the 3-nitrotyrosine/tyrosine ratio significantly increased with advancing age, whereas the tyrosine concentration was unaltered. In patients with AD, the 3-nitrotyrosine concentration and the 3-nitrotyrosine/tyrosine ratio increased significantly (>six-fold) compared with controls of similar age, and increased significantly with decreasing cognitive functions, whereas the tyrosine concentration did not change. These findings suggest that an activation of tyrosine nitration, increase in nitrated tyrosine-containing proteins, and/or its degradation may be involved in brain aging and play an important role in the pathogenesis of AD.     

Increase in oxidized NO products and reduction in oxidized glutathione in cerebrospinal fluid from patients with sporadic form of amyotrophic lateral sclerosis

To determine the role of free radical mechanisms in the pathogenesis of amyotrophic lateral sclerosis (ALS), cerebrospinal fluid concentrations of oxidized nitric oxide (NO) products (nitrite and nitrate) and reduced and oxidized forms of glutathione (GSH and GSSG, respectively) were compared between patients with the sporadic form of ALS (SALS) and controls. In the SALS patients, the nitrate levels were significantly higher (by 73%) in contrast to remarkably lower GSSG/GSH ratio, approximately 3-fold, compared to controls. These results suggest that NO production or oxidation is activated in SALS patients, leading to a decrease in superoxide radicals to oxidize GSH. The subsequent generation of a highly reactive anion, peroxynitrite, may play a causal role in the pathogenesis of SALS.