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Enhanced expression of cyclooxygenase-2 in glaucomatous dog eyes 总被引：4，自引：1，他引：3
Objective Cyclooxygenase‐2 (COX‐2)‐derived prostaglandins (PGs) are shown to play important pathophysiologic roles in various disease states. Recently, the effectiveness of topical PGs in reducing intraocular pressure (IOP) has stimulated further interest in the physiologic function of COX‐2 and PGs in normal and glaucomatous eyes. Therefore, we investigated the cell‐type distribution and expression of COX‐2 in normal and glaucomatous dog eyes. Procedures Using isoform‐specific antibodies, we immunohistochemically evaluated COX‐2 expression in formalin‐fixed and paraffin‐embedded normal (n = 5) and glaucomatous (n = 17) dog eyes. Results In the normal eyes, only minimal COX‐2 immunoreactivity was observed in the ciliary epithelium. In the glaucomatous eyes, COX‐2 expression was further observed in the cornea and corneoscleral limbus. In the cornea, moderate to strong COX‐2 expression was observed in all corneal layers (epithelium, stromal cells and endothelium), with the greatest expression present in the epithelial layer. In the corneoscleral limbus area, COX‐2 immunoreactivity was noted in the stromal cells of sclera, trabecular meshwork and endothelial cells of the angular aqueous plexus. Conclusions Increased expression of COX‐2 in dog glaucomatous eyes suggests that COX‐2‐derived PGs may have a potential role in the pathogenesis of canine glaucoma. 相似文献
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Kristina M. Stanfield K. Nasir Khan Michael R. Gralinski 《Veterinary immunology and immunopathology》2001,80(3-4):309-314
Prostaglandins have diverse roles in the cardiovascular system mediating both physiologic and inflammatory responses. Two cyclooxygenase isoforms, cyclooxygenase-1 and cyclooxygenase-2, catalyze prostaglandin production. In many tissues and cell types studied, cyclooxygenase-1 is constitutively active whereas cyclooxygenase-2 expression is primarily responsible for prostaglandin production during inflammation. However, little information exists concerning which isoform is responsible for prostaglandin-mediated effects in the heart. We examined cyclooxygenase-1 and cyclooxygenase-2 expression in heart and vascular tissue of dogs using isoform-specific antibodies. In addition, tissues from dogs treated with naproxen (5–10 mg/kg/day), an inhibitor of prostaglandin production were also examined. Cyclooxygenase-1 expression was evident in endothelial cells of the microvasculature of the heart, aorta and renal artery. Cyclooxygenase-1 expression was also found in fibrocytes of the tricuspid valve and in the chordae tendinae. Animals treated with naproxen exhibited a similar pattern and intensity of cyclooxygenase-1 staining. No cyclooxygenase-2 expression was evident in cardiac tissue. However, minimal cyclooxygenase-2 immunoreactivity was present in the vascular endothelial cells of small myocardial blood vessels located in several regions of the heart as well as in endothelial cells of the aorta. These data may expand our understanding of the effects of non-steroidal anti-inflammatory drugs on cardiac function. 相似文献
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Mammalian cells contain two related but unique isoforms of cyclooxygenase (COX-1 and COX-2). COX-1 is expressed constitutively in a majority of tissues and is involved in the production of prostaglandins (PGs) that modulate normal physiologic functions. COX-2 is inducible by various stimuli and is involved in the production of PGs that modulate physiologic events in development, cell growth, and inflammation. With the exception of peribronchial glands and chondrocytes of peribronchial cartilage, COX-2 is not detectable in the normal lung of nonhuman primates. We evaluated COX-2 expression by immunohistochemical methods in the inflammatory lesions of two cynomolgus monkeys (Macaca fascicularis) with acute severe pneumonia. Both monkeys exhibited acute severe bronchopneumonia; histologically, lung lesions were characterized by infiltration of large numbers of neutrophils and fewer macrophages, mild bronchial epithelial hyperplasia, and slight type-2 pneumocyte hyperplasia. In both monkeys, mild to marked COX-2 immunoreactivity was detected within the cytoplasm of macrophages, bronchial epithelial cells, type-2 pneumocytes, and endothelial cells of blood vessels. No COX-2 immunoreactivity was detectable in the neutrophils that constituted >90% of the inflammatory cells. These observations suggest that in acute inflammatory lung lesions in nonhuman primates 1) COX-2 is induced in the bronchial and alveolar epithelial cells, 2) macrophages are the primary inflammatory cells that exhibit COX-2, and 3) neutrophils do not express COX-2. 相似文献
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Cartilaginous fish are the phylogenetically oldest living organisms known to possess components of the vertebrate adaptive immune system. Key to their immune response are heavy-chain, homodimeric immunoglobulins called new antigen receptors (IgNARs), in which the variable (V) domains recognize antigens with only a single immunoglobulin domain, akin to camelid heavy-chain V domains. The 1.45 angstrom resolution crystal structure of the type I IgNAR V domain in complex with hen egg-white lysozyme (HEL) reveals a minimal antigen-binding domain that contains only two of the three conventional complementarity-determining regions but still binds HEL with nanomolar affinity by means of a binding interface comparable in size to conventional antibodies. 相似文献
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Pejchal R Doores KJ Walker LM Khayat R Huang PS Wang SK Stanfield RL Julien JP Ramos A Crispin M Depetris R Katpally U Marozsan A Cupo A Maloveste S Liu Y McBride R Ito Y Sanders RW Ogohara C Paulson JC Feizi T Scanlan CN Wong CH Moore JP Olson WC Ward AB Poignard P Schief WR Burton DR Wilson IA 《Science (New York, N.Y.)》2011,334(6059):1097-1103
The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of antigen-binding fragments (Fabs) PGT 127 and 128 with Man(9) at 1.65 and 1.29 angstrom resolution, respectively, and glycan binding data delineate a specific high mannose-binding site. Fab PGT 128 complexed with a fully glycosylated gp120 outer domain at 3.25 angstroms reveals that the antibody penetrates the glycan shield and recognizes two conserved glycans as well as a short β-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificity. Furthermore, our data suggest that the high neutralization potency of PGT 127 and 128 immunoglobulin Gs may be mediated by cross-linking Env trimers on the viral surface. 相似文献
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Huang CC Tang M Zhang MY Majeed S Montabana E Stanfield RL Dimitrov DS Korber B Sodroski J Wilson IA Wyatt R Kwong PD 《Science (New York, N.Y.)》2005,310(5750):1025-1028
The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is immunodominant and contains features essential for coreceptor binding. We determined the structure of V3 in the context of an HIV-1 gp120 core complexed to the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding of gp120 to cell-surface CD4 would position V3 so that its coreceptor-binding tip protrudes 30 angstroms from the core toward the target cell membrane. The extended nature and antibody accessibility of V3 explain its immunodominance. Together, the results provide a structural rationale for the role of V3 in HIV entry and neutralization. 相似文献
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Saphire EO Parren PW Pantophlet R Zwick MB Morris GM Rudd PM Dwek RA Stanfield RL Burton DR Wilson IA 《Science (New York, N.Y.)》2001,293(5532):1155-1159
We present the crystal structure at 2.7 angstrom resolution of the human antibody IgG1 b12. Antibody b12 recognizes the CD4-binding site of human immunodeficiency virus-1 (HIV-1) gp120 and is one of only two known antibodies against gp120 capable of broad and potent neutralization of primary HIV-1 isolates. A key feature of the antibody-combining site is the protruding, finger-like long CDR H3 that can penetrate the recessed CD4-binding site of gp120. A docking model of b12 and gp120 reveals severe structural constraints that explain the extraordinary challenge in eliciting effective neutralizing antibodies similar to b12. The structure, together with mutagenesis studies, provides a rationale for the extensive cross-reactivity of b12 and a valuable framework for the design of HIV-1 vaccines capable of eliciting b12-like activity. 相似文献
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Calcium currents in skeletal muscle fibers of an insect, Carausius morosus, inactivate under depolarization. This inactivation depends on the current being carried across the membrane by calcium ions, rather than strontium or bariumions. 相似文献
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Huang CC Lam SN Acharya P Tang M Xiang SH Hussan SS Stanfield RL Robinson J Sodroski J Wilson IA Wyatt R Bewley CA Kwong PD 《Science (New York, N.Y.)》2007,317(5846):1930-1934
The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (alpha-helix) and 412d (extended loop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system. 相似文献