心钠素免疫反应在豚鼠耳蜗中的整体分布

目的 :研究豚鼠耳蜗中心钠素 (ANP)免疫反应的分布状态 ,为探讨ANP在耳蜗中的作用提供形态学基础。方法 :采用免疫组织化学ABC法检测ANP在正常豚鼠耳蜗各组织中的分布特征。结果 :在耳蜗 1～ 4回的血管纹、螺旋缘、Corti’s器、螺旋神经节和中间阶外壁的螺旋韧带均发现有ANP反应 (ANP IR)阳性产物 ;而耳蜗骨壁、前庭膜、鼓阶外壁的螺旋韧带和鼓阶的下壁ANP IR为阴性。结论 :耳蜗中的ANP在内耳淋巴液的生成和声信号的传导以及耳蜗血流量的调节等方面可能担负着重要的作用     

New Zealand white rabbits immunized with RNA-complexed total histones develop an autoimmune-like response.

The antibody response of rabbits immunized with a total histone mixture containing randomly coiled H1/H5, H2A, H2B, H3 and H4 devoid of DNA was investigated in direct and competitive ELISA. The antisera were tested with isolated histones and chromatin and with a series of overlapping synthetic peptides covering the entire sequences of the four core histones and two peptides of H1. It was found that the New Zealand (NZ) white rabbits immunized with the total histone (TH) mixture complexed with RNA produced IgG antibodies reacting with histones and with a number of histone peptides but not with chromatin. The antisera also contained IgG antibodies which bound components that correspond to common target antigens in autoimmune diseases such as native dsDNA, peptides of Sm-D antigen, ubiquitin, branched peptides of ubiquitinated H2A and poly(ADP-ribose). By competition experiments, it was shown that these antibodies corresponded to non-crossreacting antibody populations. New Zealand rabbits immunized with TH in the absence of RNA or random outbred rabbits immunized with the RNA-complexed histone fraction produced antibodies reacting with histone, chromatin and very few histone peptides, while no activity with non-related antigens was observed. The pattern of reactivity of antisera raised in NZ rabbits with RNA-complexed TH was found to be very similar to that observed in sera of patients with systemic lupus erythematosus while, in contrast, the antibody response was very different in NZ or outbred rabbits immunized with various native nuclear particles and with individual histones. Altered nucleosome particles rather than native nucleosomes may represent the antigenic stimulus giving rise to autoantibodies.     

Comparative analysis of biological activities of Der p I-derived peptides on Fc epsilon receptor-bearing cells from Dermatophagoides pteronyssinus-sensitive patients.

The ability of four uncoupled synthetic peptides (p52-71, p117-133, p176-187, p188-199) derived from Der p I, a major allergen from the house dust mite Dermatophagoides pteronyssinus (Dpt) to stimulate Fc epsilon R+ cells from Dpt-sensitive patients was comparatively analysed. Each free peptide may specifically stimulate basophils (Fc epsilon RI+ cells) and platelets (Fc epsilon RII+ cells) from patients with significant levels of anti-Der p I IgE antibodies; p52-71 and p117-133 appear the best cell stimulation inducers. Both concentration-dependent biological activities of Der p I-peptide on Fc epsilon R+ cells are enhanced by coupling peptide to a carrier (as human serum albumin). Interestingly each Der p I-sensitive patient tested presents an individual pattern of response to peptide. Thus, from our results it appears that different Der p I sequences could be involved in the immune response to Der p I.     

Neuraminidase- and benzalkonium chloride-dependent inhibition of basic peptide-induced rat mast cell secretion

Two types of inhibition of basic peptide-induced rat mast cell secretion are reported. Pretreatment of rat peritoneal mast cells with Vibrio comma neuraminidase, an enzyme which cleaves sialic acid from oligosaccharides, led to inhibition of 5-hydroxytryptamine release induced by the basic peptides polylysine, corticotropin_1–24 and a decapeptide sequence of human IgE. Inhibition was similarly observed when mast cells were challenged in the presence of the cationic cell membrane-active substance benzalkonium chloride. It is postulated that both of these experimental procedures inhibit basic peptide-induced secretion by depletion of cell surface negative charge. Sialic acid itself does not act as a specific receptor for basic peptides, since a molar excess of sialic acid in free solution failed to inhibit secretion by binding to basic peptides in the fluid phase.     

Atrial amyloid deposits in the failing human heart display both atrial and brain natriuretic peptide-like immunoreactivity

Atrial amyloid deposits are common in the ageing human heart and contain alpha-atrial natriuretic peptide (proANP99-126) immunoreactivity. However, atrial myocytes secrete both amino and carboxy terminal fragments of the ANP prohormone (proANP1-126) and also express an homologous, but separate brain natriuretic peptide (BNP). Characteristic amyloid deposits were identified in the atria of 9/22 patients (26-63 years of age) with end-stage heart failure. Amyloid fibrils displayed immunoreactivity for both amino and carboxy terminal fragments of proANP1-126 and for the distinct BNP sequence. As in other endocrine organs, both mature and precursor peptide sequences appear to be constituents of amyloid fibrils. Whilst immunoreactivity for cardiac peptide hormones is co-localized in atrial amyloid deposits, it is uncertain whether the increase in natriuretic peptide expression which accompanies cardiac failure contributes to the incidence of isolated atrial amyloidosis.     

Endocrine differentiation of extra-pulmonary small cell carcinoma demonstrated by immunohistochemistry using antibodies to PGP 9.5, neuron-specific enolase and the C-flanking peptide of human pro-bombesin

Several recent studies have confirmed the endocrine nature of small cell carcinoma of the lung. In extra-pulmonary sites, small cell 'undifferentiated' carcinomas have classical morphological features similar to their pulmonary counterpart. We therefore investigated, using immunocytochemistry, the possibility that the non-pulmonary neoplasms may also be endocrine in nature. Sections of 29 small cell carcinomas from oesophagus, stomach, larynx, colon and urinary bladder were immunostained using antisera to protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), cytokeratin, leucocyte common antigen and peptides including bombesin, the C-flanking peptide of human probombesin, adrenocorticotrophic hormone, neurotensin, calcitonin and pancreatic polypeptide. All the tumours showed immunoreactivity for at least one of the two general endocrine markers PGP 9.5 and NSE. Twenty-three of the 29 cases were immunoreactive for PGP 9.5, 27 for NSE. All were positive for cytokeratin and negative for leucocyte common antigen. Of the regulatory peptides, immunoreactivity was obtained with antisera to bombesin (one case), the C-flanking peptide of human pro-bombesin (14 cases), adrenocorticotrophic hormone (one case) and calcitonin (three cases). No PGP 9.5-, NSE- or peptide-like immunoreactivity was detected in 25 control tumours from similar sites, including lymphomas and poorly differentiated tumours. These results suggest that non-pulmonary small cell carcinoma has an endocrine character.     

Content of Autoantibodies to Bradykinin and β-Amyloid1-42 as a Criterion for Biochemical Differences between Alzheimer's Dementias

We measured serum content of autoantibodies to -amyloid protein A_1-42, its neurotoxic fragment A_25-35, vasopressin, bradykinin, thrombin, antithrombin III, ₂-macroglobulin, and angiotensin II in patients with various forms of Alzheimer's dementias, including presenile and senile dementias of the Alzheimer type. The ratio of antibradykinin and anti-A_1-42 autoantibody contents differed by 39% in these patients. Our results can be used for the development of a new biochemical method for differential diagnostics of dementias of the Alzheimer type.     

Effect of hydra peptide morphogen on cyclic nucleotide levels in injured tissues

Novokuznetsk Branch, Central Research Institute of Prosthetics. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 10, pp. 486–487, October, 1989.     

Human defensins

Antimicrobial peptides are small, cationic, amphiphilic peptides of 12–50 amino acids with microbicidal activity against both bacteria and fungi. The eukaryotic antimicrobial peptides may be divided into four distinct groups according to their structural features: cysteine-free -helices, extended cysteine-free -helices with a predominance of one or two amino acids, loop structures with one intramolecular disulfide bond, and -sheet structures which are stabilised by two or three intramolecular disulfide bonds. Mammalian defensins are part of the last-mentioned group. The mammalian defensins can be subdivided into three main classes according to their structural differences: the -defensins, -defensins and the recently described -defensins. Mammalian -defensins are predominantly found in neutrophils and in small intestinal Paneth cells, whereas mammalian -defensins have been isolated from both leukocytes and epithelial cells. Recently, two novel human -defensins, human beta-defensin-3 (HBD-3), and human beta-defensin-4 (HBD-4) have been discovered. Similar to HBD-1 and HBD-2, HBD-3 has microbicidal activity towards the Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the yeasts Candida albicans and Malassezia furfur. In addition, HBD-3 kills Gram-positive bacteria such as Streptococcus pyogenes or Staphylococcus aureus, including multi-resistant S. aureus strains, and even vancomycin-resistant Enterococcus faecium. In contrast to HBD-1 and HBD-2, significant expression of HBD-3 has been demonstrated in non-epithelial tissues, such as leukocytes, heart and skeletal muscle. HBD-4 is expressed in certain epithelia and in neutrophils. Its bactericidal activity against P. aeruginosa is stronger than that of the other known -defensins. Here we present an overview of human antimicrobial peptides with some emphasis on their antifungal properties.J.J. Schneider and A. Unholzer contributed equally to this work     

The set of naturally processed peptides displayed by DR molecules is tuned by polymorphism of residue 86

The response to tetanus toxoid (TT) was studied in immune donors that carry two alleles of DR5 that differ only at DRβ residue 86: DRB1*1101 (G86, abbreviated 1101) and DRB1*1104 (V86, abbreviated 1104). A large number of TT-specific T cell clones was isolated and the epitopes recognized in association with 1101 and 1104 were mapped. We found that two epitopes (p2 and p32) can be recognized in association with both 1101 and 1104 while three epitopes (p23, p27 and p30) are recognized in association with 1101, but never in association with 1104. The sets of naturally processed self peptides displayed by 1101 and 1104 were characterized using alloreactive T cell clones. We found that all 1104 alloreactive clones recognize both 1104 and 1101, while ?30% of the alloreactive 1101 clones fail to recognize 1104. Thus it is apparent that both naturally processed TTand self peptides displayed on 1104 molecules represent a fraction of those displayed on 1101 molecules. The mechanism responsible for this differential presentation was investigated by comparing the capacity of 1101 and 1104 antigen-presenting cells to present TTor synthetic peptides to specific T cells and by measuring the binding of these peptides to DR molecules. Three sets of results suggest that V86 acts as a constraint to the binding of naturally processed peptides: (i) all 1104-restricted or alloreactive T cell clones recognize TT- or allo-epitopes presented by 1101 as well, thus ruling out a major effect of V86 as a residue determining T cell restriction specificity; (ii) presentation of naturally processed peptides correlates in general with the capacity of long synthetic peptides to bind to 1101 or 1104 and (iii) while the naturally processed p30 epitope discriminates between 1101 and 1104, a short synthetic peptide binds equally well to and is comparably recognized in association with both 1101 and 1104. Taken together these results suggest that the natural polymorphism at residue 86 might be a molecular switch that finely tunes the complexity of the peptide collection presented on DR molecules.