Membrane-bound Steel factor induces more persistent tyrosine kinase activation and longer life span of c-kit gene-encoded protein than its soluble form

Alternative splicing of exon 6 results in the production of two isoforms of Steel factor (SLF): the membrane-bound and soluble forms. To investigate differences in the kinetics of c-kit tyrosine kinase activated by these two isoforms, we used a stromal cell line (SI/SI4) established from SI/SI homozygous murine embryo fetal liver and its stable transfectants containing either hSCF248 cDNA (including exon 6; secreted form) or hSCF220 cDNA (lacking exon 6; membrane-bound form) as the source of each isoform. Interaction of factor dependent myeloid cell line MO7e with stromal cells producing either isoform resulted in activated c-kit tyrosine kinase and induction of the same series of tyrosine phosphorylated cellular proteins in MO7e cells. However, SI4- h220 (membrane-bound form) induced more persistent activation of c-kit kinase than SI4-h248 (soluble form) did. Flow cytometric analysis and pulse-chase studies using [35S]methionine showed that SI4-h248 induced rapid downmodulation of cell-surface c-kit expression and its protein degradation in MO7e cells, whereas SI4-h220 induced more prolonged life span of c-kit protein. Addition of soluble recombinant human SLF to SI4- h220 cultures enhanced reduction of cell-surface c-kit expression and its protein degradation. Because the kinetics of c-kit inactivation strikingly fits with the protein degradation rates of c-kit under the conditions described above, rapid proteolysis of c-kit protein induced by soluble SLF stimulation may function as a "turn-off switch" for activated c-kit kinase.     

Tumor necrosis factor receptor I from patients with tumor necrosis factor receptor-associated periodic syndrome interacts with wild-type tumor necrosis factor receptor I and induces ligand-independent NF-kappaB activation

OBJECTIVE: To investigate the molecular consequences of expressing mutated forms of tumor necrosis factor receptor I (TNFRI) as found in patients with TNFR-associated periodic syndrome (TRAPS). METHODS: We cloned and expressed full-length wild-type (WT) and T50K and P46L variants of TNFRI using a new tightly regulated doxycycline-dependent expression system. This system enabled the study of molecular interactions between these receptors at both physiologic and pathophysiologic levels of expression. RESULTS: We used chemical crosslinking on the cell surface to show that WT and mutant forms of TNFRI, derived from TRAPS patients, interact in the absence of TNF ligand. Doxycycline-controlled up-regulation of one TNFRI allele, either WT or mutant, caused down-regulation of the other allele, indicating dynamic control of cell surface assembly. We also demonstrated that increased expression of mutant TNFRI (T50K) was associated with a parallel increase in NF-kappaB p65 (RelA) subunit activation, which did not occur with increased expression of WT TNFRI. CONCLUSION: The T50K TRAPS-related variant is capable of sustaining inappropriate NF-kappaB activation, resulting in persistent auto-inflammation in target organs such as skin, synovial membrane, and the central nervous system. We conclude that some of the inflammatory processes seen in TRAPS do not involve direct interaction of TNF with its receptors, but that other proinflammatory mechanisms capable of up-regulating TNFRI expression may cause cellular activation through the NF-kappaB signaling pathway.     

Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells

Protein glycosylation is an important posttranslational process, which regulates protein folding and functional expression. Studies have shown that abnormal glycosylation in tumor cells affects cancer progression and malignancy. In the current study, we have identified sialylated proteins using an alkynyl sugar probe in two different lung cancer cell lines, CL1-0 and CL1-5 with distinct invasiveness derived from the same parental cell line. Among the identified sialylated proteins, epidermal growth factor receptor (EGFR) was chosen to understand the effect of sialylation on its function. We have determined the differences in glycan sequences of EGFR in both cells and observed higher sialylation and fucosylation of EGFR in CL1-5 than in CL1-0. Further study suggested that overexpression of sialyltransferases in CL1-5 and α1,3-fucosyltransferases (FUT4 or FUT6) in CL1-5 and A549 cells would suppress EGFR dimerization and phosphorylation upon EGF treatment, as compared to the control and CL1-0 cells. Such modulating effects on EGFR dimerization were further confirmed by sialidase or fucosidase treatment. Thus, increasing sialylation and fucosylation could attenuate EGFR-mediated invasion of lung cancer cells. However, incorporation of the core fucose by α1,6-fucosylatransferase (FUT8) would promote EGFR dimerization and phosphorylation.     

Crystal structure of human stem cell factor: implication for stem cell factor receptor dimerization and activation

Stem cell factor (SCF) plays important roles in hematopoiesis and the survival, proliferation, and differentiation of mast cells, melanocytes, and germ cells. SCF mediates its biological effects by binding to and activating a receptor tyrosine kinase designated c-kit or SCF receptor. In this report we describe the 2.3-A crystal structure of the functional core of recombinant human SCF. SCF is a noncovalent homodimer composed of two slightly wedged protomers. Each SCF protomer exhibits an antiparallel four-helix bundle fold. Dimerization is mediated by extensive polar and nonpolar interactions between the two protomers with a large buried surface area. Finally, we have identified a hydrophobic crevice and a charged region at the tail of each protomer that functions as a potential receptor-binding site. On the basis of these observations, a model for SCF small middle dotc-kit complex formation and dimerization is proposed.     

Risk of tuberculosis is higher with anti–tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three‐year prospective french research axed on tolerance of biotherapies registry

Objective

Tuberculosis (TB) is associated with anti–tumor necrosis factor (anti‐TNF) monoclonal antibody (mAb) therapy, but whether this association is drug‐specific remains a concern. Our objective was to describe cases of TB associated with anti‐TNF mAb therapy, identify risk factors, and estimate the incidence.

Methods

We conducted an incidence study and a case–control analysis to investigate the risk of newly diagnosed TB associated with the use of anti‐TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti‐TNF mAb therapy for any indication; for each case, 2 patients treated with anti‐TNF agents served as control subjects.

Results

We collected 69 cases of TB in patients treated for rheumatoid arthritis (n = 40), spondylarthritides (n = 18), inflammatory colitis (n = 9), psoriasis (n = 1) and Behçet's disease (n = 1) with infliximab (n = 36), adalimumab (n = 28), and etanercept (n = 5). None of the patients had received correct chemoprophylactic treatment. The sex‐ and age‐adjusted incidence rate of TB was 116.7 per 100,000 patient‐years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7–15.5) and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4–25.8] and SIR 29.3 [95% CI 20.3–42.4] versus SIR 1.8 [95% CI 0.7–4.3], respectively). In the case–control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6–69.0] and OR 17.1 [95% CI 3.6–80.6], respectively). Other risk factors were age, the first year of anti‐TNF mAb treatment, and being born in an endemic area.

Conclusion

The risk of TB is higher for patients receiving anti‐TNF mAb therapy than for those receiving soluble TNF receptor therapy. The increased risk with early anti‐TNF treatment and the absence of correct chemoprophylactic treatment favor the reactivation of latent TB.

     

Lack of efficacy of a third tumour necrosis factor alpha antagonist after failure of a soluble receptor and a monoclonal antibody

OBJECTIVE: Some studies have highlighted the potential benefits of switching from infliximab to etanercept, or after failure of one or the other treatment. To our knowledge, no study has assessed the potential benefits of using the three anti-TNF-alpha agents that are currently available. The objective of this retrospective study was to assess the response to treatment in RA patients who had received the three anti-TNF-alpha agents, namely infliximab, etanercept and adalimumab. METHODS: Among a cohort of 364 patients undergoing biological treatments since the year 2000, 284 had been treated with only one anti-TNF-alpha agent. Our assessment focused on the records of 70 patients who had received at least two anti-TNF-alpha agents. Twenty of the 70 patients had received all three anti-TNF-alpha agents (infliximab, etanercept and adalimumab). Effectiveness was assessed using the 28-joint Disease Activity Score (DAS28), and adverse events were reported for each anti-TNF-alpha treatment. RESULTS: Of the 70 patients who had received two anti-TNF-alpha agents, 32 had switched from an antibody to a soluble receptor; 45% of them had a good clinical response to the soluble receptor. Thirty patients had switched from a soluble receptor to an antibody; 45% of them had a good clinical response to the antibody. Only eight patients had switched from an antibody to another antibody with an efficiency score of 33%. Of the 20 patients who had received three anti-TNF-alpha agents, seven had stopped receiving the third anti-TNF-alpha agent due to lack of effectiveness. In this group of non-responders to the third anti-TNF-alpha treatment, all patients except one had stopped receiving the two previous anti-TNF-alpha agents, without adverse events, for lack of effectiveness. These patients were deemed resistant to anti-TNF-alpha therapy. CONCLUSIONS: Resistance to anti-TNF-alpha agents is rare. The lack of effectiveness of a soluble receptor and of one of the anti-TNF-alpha antibodies predicts the lack of effectiveness of the third anti-TNF-alpha treatment.     

Differential stimulation of c-Kit mutants by membrane-bound and soluble Steel Factor correlates with leukemic potential

The authors investigated the roles of PI3-kinase and PLC-gamma in stimulation by Steel Factor (SLF) through c-Kit. c-Kit mutants YF719, YF728, and a YF719/YF728 double mutant were expressed in 32D myelomonocytic cells. KitYF719 fails to recruit PI3-kinase after stimulation with SLF, whereas KitYF728 fails to stimulate PLC-gamma phosphorylation or mobilize Ca(++). Both single mutants responded mitogenically to soluble SLF (sSLF) in a manner indistinguishable from wild type (WT), although sSLF failed to stimulate or promote the survival of cells expressing the double mutant. In contrast, although cells expressing WT or YF719 were mitogenically stimulated by membrane-bound SLF (mSLF), stimulation of cells expressing KitYF728 was impaired. Similarly, cells expressing WT or YF719 receptors were stimulated by plate-bound anti-Kit antibodies, whereas cells expressing the YF728 receptor were not stimulated. Neomycin sulfate, a PLC antagonist, inhibited cells expressing YF719 receptors stimulated by sSLF. Neomycin also inhibited cells expressing the WT receptor that were stimulated by mSLF or immobilized anti-Kit antibodies but did not inhibit stimulation of cells expressing WT or YF719 receptors by sSLF. 32D cells expressing KitWT, KitYF719, or KitYF728 were injected into mice and the presence of cells was evaluated by colony assays 6 to 7 weeks later. Although both KitWT and KitYF719 expressing cells could be recovered from the spleen and bone marrow, recovery of KitYF728 cells from these organs was severely reduced. These results indicate that Kit tyrosine 728 is of particular importance for mitogenic stimulation by mSLF or immobilized ligand and is required for full maintenance of cells in vivo, likely through activation of PLC-gamma. (Blood. 2000;96:3734-3742)     

Anti-erythropoietin receptor monoclonal antibody: epitope mapping, quantification of the soluble receptor, and detection of the solubilized transmembrane receptor and the receptor-expressing cells

A hybridoma cell line producing the monoclonal antibody against erythropoietin receptor (EpoR) was established using the soluble ectodomain of mouse erythropoietin receptor (sEpoR) as an antigen. The monoclonal antibody termed 1G3 bound to the denatured sEpoR. Epitope mapping with peptide library revealed that 1G3 recognized the amino terminal region including the hexapeptide (positions 6 to 11; LeuProAspProLysPhe). The amino acid sequence in this hexapeptide was identical in mice, rats, and humans, and therefore 1G3 bound to EpoR from all of these sources. Using 1G3, we evaluated sEpoR by a sandwich enzyme-linked immunoassay, and EpoR in the solubilized membrane preparation was detected by Western blotting. The cells expressing EpoR were identified with immunochemical staining. We confirmed the presence of EpoR in a neuronal cell line and PC12 cells, and EpoR was expressed in primary cultured hippocampal neurons.     

Preferential self-association of basic fibroblast growth factor is stabilized by heparin during receptor dimerization and activation.

Central to signaling by fibroblast growth factors (FGFs) is the oligomeric interaction of the growth factor and its high-affinity cell surface receptor, which is mediated by heparin-like polysaccharides. It has been proposed that the binding of heparin-like polysaccharides to FGF induces a conformational change in FGF, resulting in the formation of FGF dimers or oligomers, and this biologically active form is 'presented' to the FGF receptor for signal transduction. In this study, we show that monomeric basic FGF (FGF-2) preferentially self-associates and forms FGF-2 dimers and higher-order oligomers. As a consequence, FGF-2 monomers are oriented for binding to heparin-like polysaccharides. We also show that heparin-like polysaccharides can readily bind to self-associated FGF-2 without causing a conformational change in FGF-2 or disrupting the FGF-2 self-association, but that the bound polysaccharides only additionally stabilize the FGF-2 self-association. The preferential self-association corresponds to FGF-2 translations along two of the unit cell axes of the FGF-2 crystal structures. These two axes represent the two possible heparin binding directions, whereas the receptor binding sites are oriented along the third axis. Thus, we propose that preferential FGF-2 self-association, further stabilized by heparin, like "beads on a string," mediates FGF-2-induced receptor dimerization and activation. The observed FGF-2 self-association, modulated by heparin, not only provides a mechanism of growth factor activation but also represents a regulatory mechanism governing FGF-2 biological activity.     

Erythropoiesis‐driven regulation of hepcidin in human red cell disorders is better reflected through concentrations of soluble transferrin receptor rather than growth differentiation factor 15

Growth differentiation factor 15 (GDF‐15) is a bone marrow‐derived cytokine whose ability to suppress iron regulator hepcidin in vitro and increased concentrations found in patients with ineffective erythropoiesis (IE) suggest that hepcidin deficiency mediated by GDF‐15 may be the pathophysiological explanation for nontransfusional iron overload. We aimed to compare GDF‐15 production in anemic states with different types of erythropoietic dysfunction. Complete blood counts, biochemical markers of iron status, plasma hepcidin, GDF‐15, and known hepcidin regulators [interleukin‐6 and erythropoietin (EPO)] were measured in 87 patients with red cell disorders comprising IE and hemolytic states: thalassemia, sickle cell anemia, and cobalamin deficiency. Healthy volunteers were also evaluated for comparison. Neither overall increased EPO, nor variable GDF‐15 concentrations correlated with circulating hepcidin concentrations (P = 0.265 and P = 0.872). Relative hepcidin deficiency was found in disorders presenting with concurrent elevation of GDF‐15 and soluble transferrin receptor (sTfR), a biomarker of erythropoiesis, and sTfR had the strongest correlation with hepcidin (r_S = ?0.584, P < 0.0001). Our data show that high concentrations of GDF‐15 in vivo are not necessarily associated with pathological hepcidin reduction, and hepcidin deficiency was only found when associated with sTfR overproduction. sTfR elevation may be a necessary common denominator of erythropoiesis‐driven mechanisms to favor iron absorption in anemic states and appears a suitable target for investigative approaches to iron disorders. Am. J. Hematol. 89:385–390, 2014. © 2013 Wiley Periodicals, Inc.     

Human leukocyte peroxidase: activity of a soluble and membrane-bound enzyme form in normal persons and patients with neuronal ceroid-lipofuscinosis.

Human leukocytes contain a peroxidase fraction soluble in 0.1 M phosphate buffer and an insoluble peroxidase component with 10--15 times higher specific activity which can be extracted by 0.1 M phosphate buffer + 0.2% Triton X-100 + 0.2% sodium taurocholate and sonication. Both enzyme components have been estimated spectrophotometrically with the substrate hydrogen peroxide (final concentration 1 mM) and the hydrogen donor p-phenylenediamine (final concentration 28-55 mM) within the first 60 sec. The pH-optimum of the soluble and membrane-bound leukocyte peroxidase is at pH 7.0 with a second smaller peak at pH 5.5. Using 0.2 M boric acid/0.05 M sodium borate buffer (pH 7.6) instead of phosphate buffer a 40%-50% increase of enzyme activity can be achieved. In two patients with the juvenile form of neuronal ceroid-lipofuscinosis (type Spielmeyer-Vogt) the activity of soluble leukocyte peroxidase was considerably reduced, in one patient with the late infantile form (type Jansky-Bielschowsky) the activity was just below the normal range, and in two patients with the adult form (type Kuf) activity was normal. In all patients the activity of membrane-bound leukocyte peroxidase was not significantly altered. Only one of four heterozygotes for the juvenile type had deficient values of the soluble enzyme. The variability of the peroxidase findings in patients and carriers with neuronal ceroid-lipofuscinosis make it uncertain whether this represents the primary enzymic defect.     

A monoclonal antibody recognizing human cancers with amplification/overexpression of the human epidermal growth factor receptor

Epidermal growth factor receptor (EGFR) has attracted considerable attention as a target for cancer therapy. Wild-type (wt)EGFR is amplified/overexpressed in a number of tumor types, and several mutant forms of the coding gene have been found, with DeltaEGFR, a deletion mutation lacking exons 2-7 of the external domain, being the most common and particularly associated with glioblastoma. We generated monoclonal antibodies (mAbs) against NR6(DeltaEGFR) (mouse fibroblast line NR6 transfected with DeltaEGFR). mAb 806 with selective reactivity for NR6(DeltaEGFR) in mixed hemadsorption assays, fluorescence-activated cell sorting, Western blot, and immunohistochemistry was analyzed in detail and compared with mAbs 528 (anti-wtEGFR) and DH8.3 (anti-DeltaEGFR). In xenograft tumors and molecularly pretyped glioblastomas, the reactivity pattern was as follows: 528 reactive with amplified and nonamplified wtEGFR; DH8.3 reactive with DeltaEGFR; and 806 reactive with amplified/overexpressed wtEGFR (with or without DeltaEGFR). In normal tissues, 528 but not DH8.3 or 806 was widely reactive with many organs, e.g., liver expressing high EGFR levels. In glioblastoma and non-CNS tumor panels, 806 was reactive with a high proportion of glioblastomas and a substantial number of epithelial cancers of lung and of head and neck. DH8.3 reactivity was restricted to DeltaEGFR-positive glioblastoma. Thus, 806 represents a category of mAbs that recognizes tumors with EGFR amplification/overexpression but not normal tissues or tumors with normal EGFR levels. Our study also indicates that DeltaEGFR is restricted to glioblastoma, in contrast to other reports that this mutation is found in tumors outside the brain.     

骨髓增生异常综合征T细胞早期激活及可溶性肿瘤坏死因子受体的研究

目的　研究骨髓增生异常综合征 (MDS)外周血CD+ 4 、CD+ 8T细胞早期激活标志CD69的表达及血清、骨髓可溶性肿瘤坏死因子受体 1、2 (sTNF R1、2 )的水平及其意义。方法　在植物血凝素 (PHA) 2 0mg/L条件下进行全血细胞培养 ,于 0h和 4h分别用流式细胞仪对CD+ 4 、CD+ 8T细胞CD69的表达进行分析。用ELISA法检测血清和骨髓sTNF R1、2的水平。结果　PHA刺激前难治性贫血 (RA)与难治性贫血伴环形铁粒幼细胞增多 (RAS)CD+ 4 、CD+ 8细胞CD69的表达率分别为 8 32 %、9 88% ,难治性贫血伴原始细胞增多 (RAEB)与转变中的RAEB(RAEB T)CD+ 8细胞CD69的表达率为7 92 %。PHA刺激后MDS患者CD+ 4 、CD+ 8细胞表达CD69明显增强 ,RA +RAS为 5 3 4 6 %、5 1 6 3% ;RAEB +RAEB T为 4 2 93%、4 1 96 % ,CD+ 4 与CD+ 8细胞CD69的表达率相似。MDS两种sTNF R1水平均明显升高 ,RA +RAS组sTNF R1血清为 (1 5 8± 0 6 8) μg/L ,骨髓为 (2 10± 0 2 6 ) μg/L ;sTNF R2血清为 (1 4 1± 0 5 0 ) μg/L ,骨髓为 (1 95± 0 6 4 ) μg/L ;RAEB +RAEB T组sTNF R1血清为 (2 6 2± 2 5 5 ) μg/L ,骨髓为 (3 12± 0 6 7) μg/L ;sTNF R2血清为 (1 96± 0 5 6 ) μg/L ,骨髓为(3 0 9± 0 6 2 ) μg/L。血清sTNF R2水平与PHA刺激     

Adduction of soluble proteins with malondialdehyde-acetaldehyde (MAA) induces antibody production and enhances T-cell proliferation

BACKGROUND: The alcohol metabolites malondialdehyde and acetaldehyde can combine to form stable adducts (MAA) which are found in the livers of humans and rats after significant alcohol ingestion. While adducted proteins induce antibody responses in the absence of adjuvants, the mechanisms by which these responses occur are unknown. Thus, it was the purpose of these studies to investigate how MAA modification stimulates antibody and T-cell responses in the absence of adjuvants. METHODS: Hen egg lysozyme (HEL) was modified with increasing levels of MAA and was used as an immunogen, and antibody and T-cell responses were determined. The role of scavenger receptors in the immunogenicity of MAA-adducted proteins was also investigated. RESULTS: Maximum antibody response was induced after immunization with 1.8 nM MAA/nM HEL, and was primarily an IgG1 response to HEL as determined by inhibition ELISAs. T-cell proliferative responses after immunization with HEL-MAA were solely to HEL. Immunization with a scavenger receptor ligand in conjunction with HEL-MAA increased the predominant IgG1 response and sharply decreased the IgG2a response by approximately 50%. Binding of HEL-MAA by splenocytes was determined by flow cytometry to be approximately 15% greater than HEL alone, showing a doubling of the geometric mean fluorescence. Also, most of the cells that bound HEL-MAA were class II positive, indicating that antigen-presenting cells can bind the MAA-adducted HEL, and potentially initiate immune responses. CONCLUSIONS: MAA modification of proteins induces antibody and T-cell proliferative responses in vivo. Initial studies suggest that these responses may be mediated by scavenger receptors that recognize MAA-adducted proteins. This suggests a mechanism by which proteins modified with oxidative products associated with chronic ethanol consumption may alter immune responses that may play an active role in the development and/or progression of alcoholic liver disease.     

Polyphloretin phosphate, an antagonist of thyrotropin action: evidence for an interaction with the hormone rather than the receptor

Polyphloretin phosphate (PPP) is known to be an inhibitor of bovine TSH (bTSH)-induced stimulation of the thyroid in both in vivo and in vitro assays. The present studies were undertaken to delineate the mechanism of these effects. A high molecular weight PPP preparation strongly inhibited both the binding of 125I-labeled bTSH [( 125I]bTSH) to human thyroid membranes and the stimulation of adenylate cyclase evoked by bTSH therein. Inhibition of bTSH-induced adenylate cyclase activity by PPP was evident both in the absence and the presence of NaCl (150 mM) in the incubation medium. Incubation of membranes with PPP, followed by its removal, did not affect subsequent binding of [125I]bTSH, indicating that PPP did not bind firmly to or damage the TSH receptor. Gel chromatography on Sephadex G-100 revealed that [125I]bTSH incubated with PPP eluted earlier than [125I]bTSH alone, indicating that PPP had formed a higher molecular weight complex with [125I]bTSH. This effect could be prevented by the addition of an excess of unlabeled bTSH to the incubation mixture. Binding of [125I] bTSH in the higher molecular weight peak generated by incubation with PPP was less than half that in control specimens of [125I]bTSH. Studies with PPP were also conducted in a highly sensitive assay that employs cultured porcine thyroid cells and measures the cAMP response induced by bTSH. The inhibitory effect of PPP on bTSH-induced cAMP accumulation was also evident in this assay. However, the presence of divalent cations Ca++ and Mg++ in the assay medium greatly diminished the inhibitory effect of PPP. Similarly, addition of Ca++ and Mg++ to the incubation medium greatly reduced or abolished the inhibitory effect of PPP on [125I]bTSH binding. Both effects of these salts to lessen the inhibitory response to PPP were overcome by increasing the PPP concentration. Gel chromatographic studies revealed that Ca++ and Mg++ acted by inhibiting the formation of the high molecular weight complex of bTSH and PPP. From these findings, we conclude that PPP exerts its inhibitory effect on TSH-induced stimulatory responses in the thyroid, in vivo as well as in vitro, by forming a complex with the hormone. The complex either does not bind to TSH receptors or does so with much lower affinity.     

Fc receptor triggering induces expression of surface activation antigens and release of platelet-activating factor in large granular lymphocytes

Triggering of large granular lymphocyte (LGL) Fc receptor with a specific monoclonal antibody (AB8.28) linked to an insoluble matrix induces cell activation, as witnessed by expression of HLA class II (DR and DQ) molecules and interleukin 2 receptor. Moreover, this event is accompanied by a concomitant release of platelet-activating factor by LGL. We conclude that the Fc receptor molecule identified by mAb AB8.28 represents a trigger for LGL activation.     

重型乙型肝炎患者血浆可溶性肿瘤坏死因子受体的变化及其临床意义

目的：为了探讨重型乙型肝炎患者血浆可溶性肿瘤坏死用于受体（ｓＴＮＦαＲ）变化及其临床意义。方法：本研究采用放射免疫沉淀一聚乙二醇分析法测定了２１例重型乙型肝炎患者血浆ｓＴＮＦαＲ水平，并以１０例正常人和２０例乙型慢性活动性肝炎作对照。结果：重型乙型肝炎患者血浆ｓＴＮＦαＲ水平显著升高，其升高程度与血清胆红素含量及凝血酶原活力变化密切相关。血清胆红素含量愈高和凝血酶原活力愈低，血浆ｓＴＮＦαＲ愈高。死亡病例血浆ｓＴＮＦαＲ升高比存活者更显著。结论：检测血浆ｓＴＮＦαＲ水平可作为评估重型肝炎病情严重性和判断预后的一个新指标。