ISSN:0892-6638    

DOI:10.1096/fasebj.3.14.2591681

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

A number of studies of inflammation and of cell growth and transformation have recently converged by defining two related families of cytokines. The first, represented by macrophage inflammatory protein 1, is composed of several gene products that have been identified in activated T cells, macrophages, and fibroblasts. The biological activities of this family are still being characterized but so far include effects on neutrophils, monocytes, and hematopoietic cells. The second, represented by macrophage inflammatory protein 2, includes platelet products such as platelet factor 4 and β‐thromboglobulin as well as several other recently described gene products that have effects on a number of cell types including neutrophils, fibroblasts, hematopoietic cells, and melanoma cells. The two families are structurally related and may have evolved from a common ancestral gene that duplicated and then diverged. Their differential control and expression in a wide variety of cell types suggests that they may have multiple functions in regulating inflammation and cell growth.—Wolpe, S. D.; Cerami, A. Macrophage inflammatory proteins 1 and 2: members of a novel superfamily of cytokines.FASEB J.3: 2565‐2573; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.14.2687068

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

During phagocytosis, phagocytic cells generate superoxide and other reactive oxygen species, which are involved in antibacterial activity. However, many bacteria possess antioxidant defenses that may explain their survival in inflammatory foci. These defenses include antioxidant enzymes such as superoxide dismutase and catalase, DNA repair systems, scavenging substrates, and competition with phagocytes for molecular oxygen. These defenses are probably coordinated, and different responses occur with different reactive oxygen species.Escherichia coliandSalmonella typhimuriummutants have allowed the demonstration of a variety of critical genes for enzymatic defense and DNA repair, as well as anoxyRregulon system. In more complex systems, the conditions found in inflammatory foci, such as decreasing glucose and the production of lactate, enhance bacterial catalase production and resistance to hydrogen peroxide. Resistance and adaptation to phagocyte‐derived oxidant stress are critical aspects of bacterial pathogenesis.— Hassett, D. J.; Cohen, M. S. Bacterial adaptation to oxidative stress: implications for pathogenesis and interaction with phagocytic cells.FASEB J.3: 2574‐2582; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.14.2556311

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

The study of multidrug resistance (MDR) in tumor cell lines has led to the discovery of the plasma membrane P‐glycoprotein (Pgp) molecule. This protein functions as an energy‐dependent pump for the efflux of diverse anticancer drugs from MDR cells. It now appears that Pgp‐mediated MDR tumor cells do occur in human cancers, and that they are likely to play a role in the ultimate response of patients to chemotherapy. Chemosensitizers, compounds able to reverse the MDR phenotype, have been identified and offer the exciting possibility of improving efficacy for some non‐responsive malignancies. Surprisingly, Pgp‐like molecules can be found in evolutionarily distant species among both eukaryotes and prokaryotes. As a group, these proteins form a superfamily of ATP‐dependent transport proteins. This finding has broad implications and provides new insights into how living organisms use this fundamental transport system to regulate the trafficking of diverse molecules across biological membranes.—Juranka, P. F.; Zastawny, R. L.; Ling, V. P‐glycoprotein: multidrug resistance and a superfamily of membrane‐associated transport proteins.FASEB J.3: 2583‐2592; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.14.2574119

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Animal models of AIDS are essential for understanding the pathogenesis of retrovirus‐induced immune deficiency and encephalopathy and for development and testing of new therapies and vaccines. AIDS and related disorders are etiologically linked to members of the lentivirus subfamily of retroviruses; these lymphocytopathic lentiviruses are designated human immunodeficiency virus type 1 (HIV‐1) and human immunodeficiency virus type 2 (HIV‐2). The only animals susceptible to experimental HIV‐1 infection are the chimpanzee, gibbon ape, and rabbit but AIDS‐like disease has not yet been reported in these species. Macaques can be persistently infected with some strains of HIV‐2 but no AIDS‐like disease has resulted. It is not yet clear how suitable HIV‐infected SCID‐hu mice will be as a model for AIDS. Several subfamilies of naturally occurring cytopathic retroviruses cause immune suppression, including fatal immunodeficiency syndromes in chickens, mice, cats, and monkeys. Domestic cats suffer immunosuppression from both an oncovirus, feline leukemia virus, and a member of the lentivirus subfamily, feline immunodeficiency virus (FIV). Asian macaques are susceptible to fatal simian AIDS from a type D retrovirus, indigenous in macaques, and from a lentivirus, simian immunodeficiency virus (SIV), which is indigenous to healthy African monkeys. SIV is the animal lentivirus most closely related to HIV. Of these animal models, the lentivirus infections of cats (FIV) and macaques (SIV) appear to bear the closest similarity in their pathogenesis to HIV infection and AIDS. This review will summarize these various animal model systems for AIDS and illustrate their usefulness for antiviral therapy and vaccinology.—Gardner, M. B.; Luciw, P. A. Animal models of AIDS.FASEB J.3: 2593‐2606; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.14.2556312

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Recent advances concerning immunoprobes are described and their biotechnologic potential is emphasized. Selected examples of immunoprobes discussed include interleukin 7, genetically engineered vaccines using live bacterial carriers, and applications of monoclonal antibodies (MAb's) for understanding and controlling blood cell malignancies as well as for analysis of prokaryotic cells. The fundamental and practical interconnections of these research areas are highlighted to show, for instance, that definition of lymphoid‐cell lineages and identification of their various subsets are aided by MAb's and interleukins. On the other hand, understanding interleukins requires isolation of cell subsets. Likewise, designing vaccines presupposes a knowledge of lymphocyte subsets and of the antigenic mosaics of the pathogens against which the vaccines are directed. Dissection of antigens in cells and in infectious agents depends to a great extent on MAb's, which are also instrumental for cloning the genes encoding antigens for vaccine preparation and those encoding interleukins for large scale production of these molecules that are promising as immunotherapeutic and vaccine adjuvants. Last, brief mention is made of the uses of MAb's in prokaryotic cell biology to illustrate the long‐range impact on these immunoprobes and, consequently, how they are opening new avenues for biotechnology.—ConwaydeMacario, E. Molecular and genetic immunoprobes for biotechnology.FASEB J.3: 2607‐2614; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.14.2687069

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Catabolism of Asn‐linked glycoproteins to monosaccharides and amino acids occurs in lysosomes. Breakdown must be complete to avoid lysosomal storage diseases that occur when fragments as small as dimers are left undigested. Recent results have clarified several aspects of Asn‐linked glycoprotein catabolism in mammals. First, degradation of the oligosaccharide portion is accomplished byexo‐glycosidases, which act only from the nonreducing end of chains to release sugar monomers as products. In contrast, proteolysis can proceed from both end and internal points along the polypeptide to eventually yield free amino acids. A second important feature of the glycoprotein disassembly pathway is that the hydrolytic steps can be grouped into two sets of ordered reactions: I) stepwise hydrolysis of the major portion of the oligosaccharide chains by a set of exoglycosidases, and II) ordered disassembly of the protein and the oligosaccharide‐to‐protein linkage region. Process II can vary at a single reaction step depending on the species in which degradation takes place. Thus, the last step of reaction sequence II can be either:1) hydrolysis of the actual peptide‐to‐carbohydrate linkage, or2) removal of the reducing‐end GlcNAc from a previously freed oligosaccharide. The latter cleavage is catalyzed by the lysosomal glycosidase chitobiase. Chitobiase has been found only in humans and rats and not in other mammals (dogs, cats, goats, sheep, cats, or cattle). The hydrolytic mechanism of this enzyme is unique as it appears to be a reducing‐end glycosidase and can be viewed as an accessory step in the human and rat digestive pathways. The species that lack this enzyme likely rely on exo‐β‐d‐glucosaminidase to cleave GlcNAc from both outer chain residues and the chitobiose moiety at the protein‐to‐carbohydrate linkage.—Aronson, N. N., Jr.; Kuranda, M. J. Lysosomal degradation of Asn‐linked glycoproteins.FASEB J.3: 2615‐2622; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.14.2531691

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Chronic glucocorticoid treatment results in skeletal muscle wasting. However, if the contractile activity of muscle is increased, this effect is abated. Because the gene encoding glutamine synthetase is known to be glucocorticoid inducible, it represents an appropriate model for testing whether glucocorticoids and endurance training can exert antagonistic effects on the expression of specific genes in muscle tissue. Our data confirm that administration of hydrocortisone 21‐acetate to rats produces 2.4‐ and 5.9‐fold increases in plantaris muscle glutamine synthetase enzyme activity and mRNA, respectively. Moreover, subjecting rats to a 12‐ to 16‐wk exercise program diminishes the basal levels of these indices of glutamine synthetase expression to approximately 60% of the values observed in sedentary controls. Endurance training produces a similar effect on plantaris muscle glutamine synthetase expression in glucocorticoid‐treated animals. These data demonstrate that the therapeutic effects of exercise in counteracting muscle atrophy are associated with attenuation of expression of a glucocorticoid‐inducible gene in skeletal muscle.—Falduto, M. T.; Hickson, R. C.; Young, A. P. Antagonism by glucocorticoids and exercise on expression of glutamine synthetase in skeletal muscle.FASEB J.3: 2623‐2628; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.14.2574120

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Transepithelial fluid secretion has been postulated to account for the accumulation of fluid within hereditary and acquired renal cysts, but no such mechanism has been demonstrated in human kidney epithelium. It is shown here that transepithelial fluid secretion was stimulated by prostaglandin E1(PGE1), forskolin, 8‐Br‐cyclic AMP, and l‐methyl‐3‐isobutylxanthine in polarized monolayers of established renal cell lines (MDCK and rat glomerular epithelial cells) and in monolayer cultures derived from the cyst walls of human autosomal dominant polycystic kidney disease and from epithelial cells of normal human renal cortex. Treatment with cyclic AMP agonists caused the same cells, when dispersed within a gel matrix of type I collagen (Vitrogen), to proliferate and form spherical fluid‐filled monolayered cysts. Our findings suggest that increased intracellular cyclic AMP levels may have a critical role in the formation and expansion of hereditary and acquired renal cysts.—Mangoo‐Karim, R.; Uchic, M. E.; Grant, M.; Shumate, W. A.; Calvet, J. P.; Park, C. H.;andGrantham, J. J. Renal epithelial fluid secretion and cyst growth: the role of cyclic AMP.FASEB J.3: 2629‐2632; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.14.2480260

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Kinetics of regulation of membrane receptors for tumor necrosis factor‐α (TNF) in human breast adenocarcinoma MCF‐7 cells was investigated. When MCF‐7 cells were incubated with radioiodinated human recombinant TNF, they bound TNF specifically and accumulated it intracellularly. Preincubation of cells with native TNF up to 1 times 10−9mfor 12 h stimulated specific binding of TNF, indicating that concentrations of membrane receptors for TNF were regulated by the ligand. Accumulation of radioactivity in cells incubated with [125I]TNF proceeded at a constant rate for up to 24 h. Kinetics of binding and internalization of TNF were similar in the presence and absence of protein synthesis for at least 1 h, suggesting that the TNF receptor was either replenished from an intracellular pool of receptors or was recycled (reutilized) during the course of TNF internalization. Data were analyzed kinetically by fitting equations of compartmental models of ligand‐cell interactions with and without the term for receptor recycling. Fits were obtained only for the model with receptor recycling; absence of the term for receptor recycling resulted in physically impossible best‐fit parameter values. Analysis of the best‐fit parameters indicated that both internalization and recycling of the receptor were stimulated by the ligand.—Vuk‐Pavlović, S.; Kovach, J. S. Recycling of tumor necrosis factor‐α receptor in MCF‐7 cells.FASEB J.3: 2633‐2640; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.14.2556313

出版商:Wiley    

年代:1989

数据来源: WILEY