Interleukin-11 Overexpression and M2 Macrophage Density are Associated with Angiogenic Activity in Proliferative Diabetic Retinopathy

ABSTRACT

Purpose

To investigate the expression of IL-11 and its receptor IL-11Rα and to quantify density of CD163⁺ M2 macrophages in proliferative diabetic retinopathy (PDR).     

Soluble CD30 in pediatric patients with atopic dermatitis

Atopic dermatitis (AD) is a chronic, inflammatory skin disease in which a pathogenetic role of Th2 cells has been supposed. This study investigated the presence of soluble CD30 (sCD30), an activation marker of T-cell clones able to produce Th2-type cytokines, in sera from pediatric patients affected by AD ( n =25) with no symptoms of asthma or rhinitis. The severity of the disease was graded by both the SCORAD and Costa et al. clinical scoring systems. Serum levels of sCD30 were significantly higher in patients with AD in respect to both normal donors ( n =20) and urticaria patients ( n = 10), and a positive correlation between serum sCD30 and clinical score was found ( r =0.508; P =0.01) when AD patients were evaluated by Costa et al.'s method. Furthermore, a significant association ( r -=0.443; P =0.027) between sCD30 and serum levels of the soluble interleukin (IL)-2 receptor (sIL-2R) was observed in AD. The presence of high amounts of sCD30 in atopic patients seems to confirm the role of this molecule as an activation marker useful for in vivo evaluation of a Th2 immune response, and the correlation observed with both clinical score and sIL-2R levels indicates the role of sCD30 as an additional marker of disease activity in pediatric patients with AD.     

sVE‐cadherin and sCD146 serum levels in patients with multiple myeloma

The role of angiogenesis in multiple myeloma (MM) pathogenesis is well established. Angiogenesis is linked to the functional state of endothelial junctions that are modulated by the growth and activation of endothelial cells. CD146 and vascular endothelial‐cadherin (VE‐cadherin) are cell adhesion molecules localized at the endothelial junction. The aim of the study was to assess sVE‐cadherin and sCD146 serum levels in MM patients. Forty‐six untreated patients with MM were included in this study. In addition, 23 of 46 patients were analyzed again in partial remission after initial chemotherapy. Twenty‐two samples from healthy volunteers were evaluated as the control. There was no significant difference in sCD146 level between MM patients and the control (511 ± 177.2 vs. 460.9 ± 156.9 ng/ml respectively). In untreated MM patients, sVE‐cadherin level was significantly higher than in the control (1.36 ± 0.55 vs. 0.63 ± 0.56 ng/ml respectively; P < 0.05). In untreated MM patients, sVE‐cadherin level was significantly higher than in MM patients in partial remission (1.36 ± 0.55 vs. 0.5 ± 0.33 respectively; P < 0.05). sVE‐cadherin but not sCD146 serum level was increased in untreated MM patients and decreases after chemotherapy in patients in partial remission. VE‐cadherin may reflect intensity of angiogenesis in MM and may be useful in prognosis of response to treatment.     

Biochemical analysis of plasma-soluble invariant chains and their complex formation with soluble HLA-DR

The invariant chain (CD74) is preferentially localized in the cytoplasm and regulates the loading of exogenous derived peptides into HLA class II heterodimers. In addition, a small proportion of CD74:class II complexes is also expressed on the cell surface. We identified and quantified soluble CD74 (sCD74) molecules in the plasma and sCD74:sHLA-DR complexes by ELISA. EDTA plasma samples from 86 healthy probands were analyzed. sCD74 could be detected in all samples with a mean concentration of 1.14 relative units±1.04 SD (range 0.17-4.31). Approximately 10% of the samples had increased amounts of sCD74 (3.0 relative units). Complexes of sCD74 and sHLA-DR were detected in all samples and their quantities were positively correlated (r=0.83, p0.001) with the sCD74 concentrations. SDS-PAGE analysis of plasma samples with high sCD74 concentrations (3.0 relative units) revealed four isoforms of sCD74 with molecular weights of 45, 43, 35, 31 kDa corresponding to known sizes of intracellular CD74. However, only molecular weights of the 45 and 43 kDa isoforms of sCD74 are found complexed with sHLA-DR. Our data demonstrate, that CD74 molecules are present in their soluble form in the plasma of healthy probands and form complexes with soluble HLA-DR molecules.     

活动性肺结核患者血清Fad D9重组蛋白、sCD14-ST及单核细胞P糖蛋白水平及其临床意义

目的探讨活动性肺结核(APTB)患者血清Fad D9重组蛋白、可溶性白细胞分化抗原14亚型(sCD14-ST)、单核细胞P糖蛋白(Pgp)表达及其临床意义。 方法选取96例APTB患者(APTB组),按照肺部病灶有无空洞和病灶肺叶数分亚组。同期选择体检健康且经γ干扰素释放试验检测阴性者(健康对照组,HC组)及阳性者(结核潜伏感染组,LTBI组)各48例。比较各组血清Fad D9重组蛋白、sCD14-ST、Pgp水平。评估Fad D9重组蛋白、sCD14-ST、Pgp诊断APTB和鉴别APTB、LTBI的价值。 结果Fad D9重组蛋白、sCD14-ST、Pgp水平APTB组＞LTBI组＞HC组,且有空洞者高于无空洞者,病灶肺叶≥3个者高于＜3个者(P＜0.05)。Fad D9重组蛋白、sCD14-ST、Pgp对APTB诊断和APTB、LTBI鉴别有良好效能(P＜0.05)。 结论APTB患者血清Fad D9重组蛋白、sCD14-ST及Pgp明显升高,且与肺部病灶的严重程度有关。     

多发性硬化患者血清sCD62E的检测及意义

多发性硬化(ｍｕｌｔｉｐｌｅｓｃｌｅｒｏｓｉｓ,ＭＳ)的病因及发病机制至今未明。目前认为 ,主要是由其Ｔ细胞介导而致中枢神经系统炎性脱髓鞘的自身免疫性疾病[1] 。由于可溶性Ｅ选择素 (又称ｓＣＤ6 2Ｅ)可介导白细胞 (中性粒、单核细胞及ＣＤ4 + 记忆性Ｔ细胞)在内皮细胞表面最初的滞留和滚动 ,以及随后迁移到炎症组织 ,推测其可能与Ｔ细胞介导的中枢神经损伤有关。为此 ,我们检测了ＭＳ患者ｓＣＤ6 2Ｅ ,以探讨其在ＭＳ发病中的作用。1　对象和方法1.1　对象　ＭＳ患者 4 5例 ,包括活动期 (ＡＭＳ) 2 5例 ,稳定期(ＳＭＳ) 2 0例。男性…     

Allergen-dependent CD14 modulation and apoptosis in monocytes from allergic patients

BACKGROUND: CD14 is a most important monocyte surface molecule. Recently, it has been reported that there is an important relationship between CD14 and immunoglobulin E, and that regulation of CD14 expression is an effector mechanism mediating apoptosis of monocytes. OBJECTIVE: The present study was designed to determine whether specific allergens were able to modulate CD14 expression and apoptosis by monocytes from allergic patients or whether specific immunotherapy (IT) might affect these processes. METHODS: One group of adult allergic asthmatic patients had received IT for the previous 3 years. Another similar group was not treated with IT. We challenged peripheral blood monocytes from both groups of asthmatic patients in vitro with the specific allergen that produced clinical symptoms in asthmatic patients. The cells were also challenged with allergen to which the patients were not sensitive. Monocytes from normal subjects were also challenged with allergens. Expression of CD14 on the monocyte surface was analyzed by flow cytometry, and soluble CD14 (sCD14) in culture supernatant by enzyme-linked immunosorbent assay. The three groups of subjects were challenged with allergens, and apoptosis was analyzed by flow cytometry. RESULTS: When monocytes from non-IT-treated asthmatic patients were cultivated with the allergens to which the patients were sensitive, a significant up-regulation on the monocyte surface was observed compared with results from the healthy group (P < 0.003) and from the IT asthmatic group (P < 0.003). A significantly higher sCD14 level was observed in the culture supernatant of the monocytes from the IT asthmatic group were observed compared with those from the healthy group (P < 0.001) and those from the non-IT asthmatic group (P < 0.001). A significantly higher apoptosis level was observed in monocytes from the IT asthmatic group compared with those from the healthy group (P < 0.001) and those from the non-IT asthmatic group (<0.001). CONCLUSIONS: We present evidence that the expression of CD14 on the surface of monocytes and the apoptosis of the same cells can be modulated by an allergen-dependent mechanism. These processes can be affected by IT.     

Effect of intrajejunal elemental diet perfusion on local secretion of soluble CD4 and CD8

The effects of nutrients on the mucosal immune system are poorly understood. The aim of this work was to study the cellular mucosal immune response to intrajejunal perfusion of an elemental diet (ED) or a control (C) electrolyte solution by measuring jejunal secretion of soluble CD4 (sCD4) and sCD8. sCD4 and sCD8 are markers of helper/inducer and suppressor/cytotoxic regulatory functions of T cells, respectively. A four lumen tube with a proximal occluding balloon at the angle of Treitz was used for jejunal perfusion in seven healthy volunteers (mean age 23 years). The length of the test segment was 40 cm. The jejunum was successively perfused with C for 80 min and then with ED containing 21.3g/l of free amino acids and 104.2g/l of oligosaccharides for 100 min. Jejunal fluid and serum concentrations of sCD4 and sCD8 were measured and their jejunal outputs calculated. When compared with C perfusion, jejunal perfusion with the ED resulted in a significant increase of sCD8 but not sCD4 jejunal secretion rates. sCD8 jejunal values increased early after ED perfusion and stayed at roughly the same level during the perfusion. Serum concentrations of sCD4 and sCD8 were not modified during ED perfusion. These data support the hypothesis that ED suppresses the immunologic tone of the gut, which could explain its beneficial effect in the management of intestinal inflammatory disease.     

Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains

Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the beta 19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies.     

Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3

The aim of the present study was to evaluate levels of soluble CD 163 in sera and fluids from rheumatoid arthritis (RA) patients and elucidate the mechanism that regulates the shedding of CD163. Levels of soluble CD163 in sera and fluids from RA patients were examined by a sandwich enzyme immunoassay and Western blotting. To determine the effects of tissue inhibitors of metalloproteinase (TIMPs) on the shedding of CD163 from monocytes/macrophages, levels of soluble CD163 in cultures of monocytes/macrophages and the expression of CD163 on monocytes/macrophages in the presence or absence of TIMPs were examined by a sandwich enzyme immunoassay and flow cytometry, respectively. The clinical marker that was most associated with serum levels of soluble CD163 was levels of CRP. TIMP-3, but not TIMP-1 or TIMP-2, inhibited the shedding of CD163 from monocytes/macrophages. It was shown that serum levels of soluble CD163 are a sensitive and reliable marker to monitor activated macrophages in synovitis from RA patients and the results imply that the responsible proteinase for the shedding of CD163 is not a member of the matrix metalloproteinases, but is likely to be a member of ADAMs.