具有抑制作用的受体和细胞内的信号转导成分

细胞对受体和细胞内信号转导蛋白的功能有着严格和精确的调控 ,其目的是维持细胞的稳态 ,防止细胞接收某种过强的信号刺激导致细胞功能和代谢紊乱。　　一、受体水平的抑制和拮抗近年来的研究表明 ,一种受体可有不同的存在形式 ,如亚型或同种型 (ｉｓｏｆｏｒｍ) ,其中的一些具有拮抗配体或抑制配体功能的作用 ,它们的存在可控制信号的强度 ,使调节更加精细和准确。(一 )具有抑制作用的膜受体1 可溶性受体　膜受体中一部分以溶解或循环形式存在于血清和其他体液中 ,被称为可溶性膜受体。已发现绝大多数的细胞因子受体 ,如ＴＮＦ -α受体、…     

PRLr mRNA在人体免疫系统中的表达

目的：探讨催乳素受体（PRLr）在人体免疫系统中的表达。方法：临床获取人中枢免疫器官胸腺瘤、骨髓和外周免疫器官淋巴结、外周血单个核细胞，经RNA抽提，RT-PCR扩增PRLr mRNA的特异片段，并进行测序。结果：从胸腺瘤、骨髓、淋巴结及外周血单个核细胞均扩增出PRLr mRNA，其片段长度与预计长度一致，均为276bp，经测序证实为所需片段。结论：人中枢免疫器官胸腺瘤、骨髓以及外周免疫器官淋巴结、外周血单个核细胞存在PRLr表达，从受体角度直接证实内分泌激素PRL发挥免疫调节作用的生物学结构依据。     

脾脏切除对大鼠外周血T细胞亚群变化影响的动态观察

脾脏是直接参与细胞介导免疫调节的一个重要免疫器官,拥有全身循环T细胞的25%和B细胞的10～15%。Ts细胞的发育成熟与脾脏密切相关。切除脾脏势必导致机体细胞免疫功能的紊乱,在这方面,已有不少报道。在对脾切除术后病人的随访观察中发现,无脾患者的外周血T细胞数     

SLE免疫调节功能紊乱的机理——T细胞亚群失衡和抗淋巴细胞抗体的作用

系统性红斑狼疮(SLE)是非器官特异的自身免疫性疾病。近年来发现SLE的发病是由于患者免疫调节功能紊乱导致多种自身抗体形成和多器官损害。其中抗淋巴细胞抗体又与某类免疫调节细胞的缺失或异常有关,如CD4和CD8表型细胞的缺失或异常导致CD4~+/CD8~+细胞比例失调,HLA-DR~+CD4~+辅助/诱导T细胞选择性增加和CD4~+2H4~+和CD4~+4B4~+T细胞亚群的变化以及带CD8~+VV~+表型的反抑制T细胞(Tcs)增加导致免疫抑制功能减退,B细胞功能亢进,从而更促使自身抗体的产生;抗淋巴细胞抗体又与免疫系统的无能有关,如它能抑制T细胞的增殖和淋巴因子的诱导。因此,SLE免疫调节功能紊乱可能是由于T细胞亚群失衡和抗淋巴细胞抗体所引起。     

肝细胞生长因子生物学作用研究进展

肝细胞生长因子作用于多种类型的细胞,具有多样的生物学作用。它可刺激细胞增殖,修复组织器官的损伤,发挥有丝分裂原的作用;它可促进胚胎的发育及各类组织器官的形态发生,发挥形态发生原的作用;它还可促进细胞的迁移和侵袭,对某些组织的形成和发育及肿瘤的转移、侵袭具有重要意义。     

全身性红斑狼疮患者T淋巴细胞亚群和sIL-2R变化的观察

观察全身性红斑狼疮（SLE）患者的TI林巴细胞亚群,NK细胞及可溶性白介素2受体（sIL-2R)的变化。以了解患者细胞免疫门节紊乱的发病机制。采用流式细胞术对60例活动性SLE患者和30名对照组进行CD3 ,CD4 ,CD8 ,NK,CD4 /CD45Ra等细胞表面标志的检测;采用ELISA法检测,sIL-2R,结果表明,SLE患者外周血中CD8＋细胞增加,而细胞CD4＋,CD4＋／CD45Ra 细胞和NK细胞均减少,CD3＋细胞无明显变化,sIL-2R水平明显增高,本文的结果提示,活动性SLE患者发病与细胞免疫调节紊乱有关。     

趋化因子及其受体的功能

趋化因子是一类控制细胞定向迁移的细胞因子。其功能行使由趋化因子受体介导。通过基因敲除、抗体封闭及转基因技术已证明 ,趋化因子系统在病原体的清除、炎症反应、病原体感染、细胞及器官的发育、创伤的修复、肿瘤的形成及其转移、移植免疫排斥等方面都起着重要的作用。本文综述了趋化因子及其受体的生物学功能的研究进展     

T淋巴细胞特异性归巢受体的研究进展

T淋巴细胞特异性归巢受体是T细胞在归巢过程中所表达的特异性黏附分子，能诱导T细胞定向移动到特定组织或器官，在T细胞归巢中起着重要作用。自前已确定表达特异性归巢受体的T淋巴细胞亚群包括归巢至小肠及皮肤的T淋巴细胞，特异性归巢受体的表达是一个复杂的过程，与局部炎症组织、次级淋巴组织微环境和树突状细胞的作用等因素密切相关。     

性激素水平及主动脉雌激素受体的变化对鹌鹑动脉粥样硬化形成 …

本文探讨了高血脂，性激素及其受体与动脉粥样硬化病变之间的关系。结果表明，高血脂可影响性腺细胞３－β－羟基甾体脱氢酶含量及脂质贮存量，导致动物人性激素环境异常及动脉壁细胞雌激素受体水平改变。提示高脂血症作为ＡＳ的始动因子之一。不仅影响动脉壁细胞的脂质代谢，还可诱发机体性激素水平紊乱，从而影响动脉壁细胞雌激素受体的表达，使之生物学行为改变，促进ＡＳ的发生发展。     

受体活化及信号转导障碍与人类疾病

细胞因子及其受体的变异直接影响其功能，从而使生物体内细胞信号转导系统功能紊乱。这些紊乱性调节引起细胞内外正常的信号转导途径短路或断路，或激活异常的信号转导途径，而使其信号转导途径发生质和／或量的改变，这些改变与疾病的发生及治疗密切相关。弄清楚在某些状态下由特异性细胞因子受体介导的不同细胞因子的正常或异常的信号转导途径及它们与某些疾病的关系，对指导人类疾病的病理学分析及临床治疗具有深远的意义     

The controversial role of mast cells in fibrosis

Fibrosis is a medical condition characterized by an excessive deposition of extracellular matrix compounds such as collagen in tissues. Fibrotic lesions are present in many diseases and can affect all organs. The excessive extracellular matrix accumulation in these conditions can often have serious consequences and in many cases be life-threatening. A typical event seen in many fibrotic conditions is a profound accumulation of mast cells (MCs), suggesting that these cells can contribute to the pathology. Indeed, there is now substantialv evidence pointing to an important role of MCs in fibrotic disease. However, investigations from various clinical settings and different animal models have arrived at partly contradictory conclusions as to how MCs affect fibrosis, with many studies suggesting a detrimental role of MCs whereas others suggest that MCs can be protective. Here, we review the current knowledge of how MCs can affect fibrosis.     

Pancreatic fibrosis associated with age and ductal papillary hyperplasia

Little is known about the frequency, type and pathogenesis of fibrotic changes that may occur in the pancreas of persons without any clinically apparent or macroscopically visible pancreatic disease. We screened pancreas specimens for the presence and pattern of fibrosis, determined the relationship between fibrosis, age, and duct lesions, and studied the fibrogenic mechanisms. In 89 postmortem specimens from persons without any known pancreatic disease (age range 20–86 years), fibrosis was recorded and graded and the patients were divided into two age classes (younger or older than 60 years). In addition, we analyzed the association between ductal papillary hyperplasia [i.e., pancreatic intraepithelial neoplasia type 1B (PanIN-1B)] and fibrotic foci in the pancreatic tissue to determine the potential impact of obliterating duct lesions on pancreatic fibrosis. Finally, we studied the occurrence in the pancreas of myofibroblasts, identified on the basis of their α-SMA and desmin positivity, and determined their relationship to the fibrotic foci. Thirty-eight (44%) of 89 pancreata showed scattered foci of lobular fibrosis affecting peripheral lobuli. Fibrotic changes were significantly more common in individuals older than 60 years. Fibrotic foci were commonly associated (p<0.05) with ductal papillary hyperplasia in ducts draining fibrotic lobuli. Myofibroblasts were detected in the fibrotic foci. The “normal” pancreas develops a specific type of focally accentuated fibrosis that is highly age related. This patchy lobular fibrosis in the elderly (PLFE) was closely associated with PanIN-1B lesions in the ducts, suggesting that the narrowing of a duct due to papillary hyperplasia of the epithelium may hamper secretion and cause fibrosis of the drained lobule. The presence of myofibroblasts in association with the fibrotic foci indicates an ongoing fibrogenic process.     

Central nervous system fibrosis is associated with fibrocyte-like infiltrates

Fibrotic wall formation is essential for limiting pathogen dissemination during brain abscess development. However, little is known about the regulation of fibrotic processes in the central nervous system (CNS). Most CNS injury responses are associated with hypertrophy of resident astrocytes, a process termed reactive gliosis. Studies of fibrosis outside the CNS have identified two bone marrow-derived cell types, fibrocytes and alternatively activated M2 macrophages, as key mediators of fibrosis. The current study used bone marrow chimeras generated from green fluorescent protein transgenic mice to evaluate the appearance of these cell types and whether bone marrow-derived cells were capable of acquiring fibrotic characteristics during brain abscess development. Immunofluorescence staining revealed partial overlap between green fluorescent protein, α-smooth muscle actin, and procollagen, suggesting that a population of cells forming the brain abscess capsule originate from a bone marrow precursor. In addition, the influx of fibrocyte-like cells into brain abscesses immediately preceded the onset of fibrotic encapsulation. Fibrotic wall formation was also associated with increased numbers of alternatively activated M2 microglia and macrophages. To our knowledge, this is the first study demonstrating that bone marrow-derived infiltrates are capable of expressing fibrotic molecules during CNS inflammation.     

Cisplatin-induced renal interstitial fibrosis in neonatal rats, developing as solitary nephron unit lesions

Cisplatin (CDDP)-induced renal lesions in rats prove a useful model for analysis of the pathogenesis of post-tubular injury-renal interstitial fibrosis. This study investigated the histopathological changes in 10-day-old neonatal rats induced by a single injection of CDDP (4.5 mg/kg). Compared with age-matched controls, on postinjection (PI) days 1 to 6, the number of apoptotic cells, demonstrable with TUNEL method, was significantly increased in CDDP-treated neonates, and there was no marked epithelial necrosis nor fibrotic lesions. Fibrotic lesions began to be developed solitarily around some nephrons with dilated ducts in the corticomedullary junction on PI day 10 and the lesions became more prominent until PI day 20. The alpha-SMA-positive myofibroblastic cells were seen exclusively in the fibrotic lesions. Additionally, the numbers of macrophages reacting with EDI (specific for exudate macrophages), ED2 (for resident macrophages), and OX6 (recognizing MHC class II antigens expressed in antigen-presenting macrophages/dendritic cells) were significantly increased around the affected renal tubules. A greater immunoreaction for TGF-beta1 was seen mostly in the renal epithelial cells of CDDP-treated neonates. These findings indicated that macrophage populations and myofibrolastic cells as well as TGF-beta1 may be responsible for the production of neonatal renal interstitial fibrosis. Compared with CDDP-injected adult rats that develop extensive interstitial fibrosis (Yamate et al., J Comp Pathol, 1995), the formation of fibrotic lesions was delayed, and the lesions were limited to the area around the affected nephrons; this could be attributable to differences in renal morphology between neonates and mature kidney of adult rats.     

Co-expression of TNF alpha and IL-1 beta in human acute pulmonary fibrotic diseases: an immunohistochemical analysis

To clarify the involvement of TNF alpha and IL-1 beta in the initiation of fibrotic lung diseases, their localization was examined by immunohistochemistry. Fibrotic lung diseases observed were classified into acute and old pulmonary fibrotic changes. The acute fibrotic changes included adult respiratory distress syndrome, acute interstitial pneumonia and idiopathic pulmonary fibrosis with acute exacerbation. Acute pulmonary fibrotic changes histopathologically corresponded to a mixture of the exudative and proliferative phases of diffuse alveolar damage. Both TNF alpha and IL-1 beta were positive in the alveolar macrophages and proliferating type II pneumocytes in acute fibrotic changes. In contrast, positive cells for TNF alpha and IL-1 beta were sparse in the areas of old fibrotic change and in the normal tissue. These findings suggest that TNF alpha and IL-1 beta play an important role in the initiation of pulmonary fibrotic responses and in the architectural remodeling, irrespective of the etiology of fibrotic lung diseases.     

Intra-alveolar fibrosis of idiopathic bronchiolitis obliterans-organizing pneumonia. Cell-matrix patterns.

Idiopathic bronchiolitis obliterans-organizing pneumonia (BOOP) is characterized by air space fibrosis of unknown origin. Clinical resolution under steroid treatment suggests the removal of the fibrotic lesion. Open lung biopsies of four patients with idiopathic BOOP were studied by immunochemistry and electron microscopy. Three distinct cell-matrix patterns of intra-alveolar bud were found to represent the sequential evolution of the fibrotic process: fibrinoid inflammatory cell clusters in which immunoglobulins and procoagulant factors (fibrinogen, factors VII and X) were identified; fibroinflammatory buds in which desmin-containing fibroblasts were observed migrating, proliferating, and secreting matrix proteins; fibrotic buds in which myofibroblasts organized a loose connective matrix predominantly composed of fibronectin and type III collagen. Extending forms of fibrotic buds may join contiguous alveoli. Fibrotic bud remodeling ability is correlated to the nature and organization of the matrix components but the factors permitting intra-alveolar matrix degradation must be characterized.     

Fibronectin and glycosaminoglycan synthesis by fibrotic pig fibroblasts in primary culture

Synthesis of fibronectin and glycosamingoglycans (GAGs) was studied in fibroblasts from pigs with post-irradiation subcutaneous fibrosis. Fibrosis was developed in the femoral muscle by local gamma irradiation with a dose of 60 Gy. Normal fibroblasts were obtained from the healthy skin of the same animal. To measure GAG and fibronectin synthesis fibrotic and normal fibroblasts were labeled with 3H-glucosamine, 35S-sulfate and 35S-methionine. Fibrotic fibroblasts synthesized 2.5 times as much fibronectin as normal skin fibroblasts but total protein synthesis did not change. Parallel enhanced secretion of hyaluronic acid and dermatan sulfate into the cell culture medium were also observed. GAGs from the pericellular layer of trypsin-digested fibrotic fibroblasts exhibited increased 3H incorporation, but reduced 35S-sulfate incorporation. The largest reduction in the latter was observed for heparan sulfate. These results indicate that the fibroblasts from the well developed fibrotic tissue maintain enhanced synthesis of matrix macromolecules in primary cultures. Structural and/or metabolic changes in secreted GAGs, combined with the stimulation of tissue repair by growth factors may be responsible for the excessive deposition of collagen in post-irradiation fibrosis.     

Increased expression of epimorphin in bleomycin-induced pulmonary fibrosis in mice

Epimorphin was originally identified as a mesenchymal, cell surface-associated protein that modulates epithelial morphogenesis in embryonic organs, whereas pulmonary fibrosis is a process of wound healing, which in part mimics the process of fetal lung development. We investigated the temporal and spatial changes in the distribution of epimorphin protein and expression of its messenger RNA (mRNA) in bleomycin-induced pulmonary fibrosis in mice. Immunohistochemical analysis showed that low levels of epimorphin were present in the bronchiolar, alveolar, and vascular walls of normal adult lungs. However, from Day 7 until Day 28 after bleomycin treatment, increasing levels of epimorphin immunoreactivity were detected in the mesenchymal cells and in the extracellular matrix within intra-alveolar fibrotic lesions. Moreover, Northern blots showed corresponding increases in epimorphin mRNA expression. Re-epithelialization of epimorphin-rich intra-alveolar fibrosis was complete by Day 28 after bleomycin, and by Day 56, epimorphin immunoreactivity had declined. In situ hybridization and confocal microscopic studies confirmed expression of epimorphin mRNA by mesenchymal cells situated within early fibrotic lesions, whereas immunoelectron microscopy localized the epimorphin to the endoplasmic reticulum of the mesenchymal cells and to the basement membrane and collagen fibrils in the area. These results suggest that epimorphin may contribute to the remodeling of pulmonary fibrosis via epithelial-mesenchymal interactions.     

Canine visceral leishmaniasis as a systemic fibrotic disease

We propose that canine visceral leishmaniasis (CVL) is a systemic fibrotic disease, as evidenced by the wide distribution of fibrosis that we have found in the dogs suffering from chronic condition. The inflammatory cells apparently direct fibrosis formation. Twenty‐four cases (symptomatic dogs) were identified from a total of one hundred and five cases that had been naturally infected with Leishmania chagasi and had been documented during an epidemiological survey of CVL carried out by the metropolitan area of the municipality of Belo Horizonte, MG, Brazil. The histological criterion was intralobular liver fibrosis, as has been described previously in dogs with visceral leishmaniasis. In addition to the findings in the liver, here we describe and quantify conspicuous and systemic deposition of collagen in other organs, including spleen, cervical lymph nodes, lung and kidney of all the infected symptomatic dogs. Thus we report that there is a systematic fibrotic picture in these animals, where inflammatory cells appear to direct fibrosis in all organs that have been studied. Therefore we propose that CVL is a systemic fibrotic disease.