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1.
Monoclonal antibodies to CD2 and lymphocyte function-associated antigen 3 inhibit human thymic epithelial cell-dependent mature thymocyte activation 总被引:10,自引:0,他引:10
S M Denning D T Tuck L W Vollger T A Springer K H Singer B F Haynes 《Journal of immunology (Baltimore, Md. : 1950)》1987,139(8):2573-2578
Recent study of human thymocyte-thymic epithelial (TE) cell interactions has demonstrated that thymocytes bind to TE cells, and a consequence of this binding is the provision of accessory cell signals by TE cells for phytohemagglutinin (PHA)-induced mature thymocyte activation. In this paper we report on studies of the molecules involved in TE cell-dependent mature thymocyte activation. TE-thymocyte interactions necessary for PHA-induced thymocyte activation were inhibited by monoclonal antibodies against the cluster of differentiation (CD)2 antigen on thymocytes and lymphocyte function-associated (LFA)-3 antigen on TE cells. Inhibition of TE accessory cell signals by antibodies against CD2 (alpha CD2) and LFA-3 (alpha LFA-3) antigens occurred early on during thymocyte activation and prevented thymocyte interleukin 2 receptor expression. Further, alpha CD2 and alpha LFA-3 inhibited PHA-induced thymocyte activation in whole thymic explant cultures suggesting a significant role of the CD2 and LFA-3 antigens in thymocyte activation when accessory cell signals for PHA-induced thymocyte triggering were delivered by cells within an intact thymic microenvironment. 相似文献
2.
Arachidonic acid was incorporated into triglycerides by cultured bovine endothelial cells in a time- and concentration-dependent manner. At 75 microM or higher, more arachidonic acid was incorporated into triglycerides than into phospholipids. The triglyceride content of the cells increased as much as 5.5-fold, cytoplasmic inclusions appeared, and arachidonic acid comprised 22% of the triglyceride fatty acids. Triglyceride turnover occurred during subsequent maintenance culture; there was a 60% decrease in the radioactive arachidonic acid contained in triglycerides and a 40% decrease in triglyceride content in 6 hr. Most of the radioactivity was released into the medium as free fatty acid. The turnover of arachidonic acid, but not oleic acid in cellular triglycerides, decreased when supplemental fatty acid was added to the maintenance medium. Incorporation and turnover of radioactive arachidonic acid in triglycerides also was observed in human skin fibroblasts, 3T3-L1 cells, and MDCK cells. Other fatty acids were incorporated into triglycerides by the endothelial cells; the amounts after a 16-hr incubation with 50 microM fatty acid were 20:3 greater than 20:4 greater than 18:1 greater than 18:2 greater than 22:6 greater than 16:0 greater than 20:5. These findings indicate that triglyceride formation and turnover can play a role in the fatty acid metabolism of endothelial cells and that arachidonic acid can be stored in endothelial cell triglycerides. 相似文献
3.
Tandler Bernard Denning Carolyn R. Mandel Irwin D. Kutscher Austin H. 《Cell and tissue research》1969,94(4):555-564
Summary Human labial salivary glands, obtained by biopsy from 32 subjects, were studied by light and electron microscopy. Intranuclear inclusions, unrelated to nucleoli, were present in many of the acinar nuclei in glands from 16 of the 32 donors. More than one inclusion was sometimes observed within a single nucleus. They measured about 1 in diameter, and were stainable in a variety of ways. They were eosinophilic, some were stained by Nile blue sulphate, some were PAS-positive, and all were Feulgen-negative. They were bounded by a single membrane, which never exhibited continuity with the nuclear envelope, and they showed considerable morphological variation. The more complex inclusions consisted of alternating shells of light and dark material with tiny dense granules embedded in the latter. The intranuclear inclusions, which apparently were non-viral in origin, were in some way related to the secretory cycle of the mucous cells, since they were found only in immature cells, and never in cells in which secretory products were abundant.This work was supported in part by grants from the Henry Spenadel Trust and the Max C. Fleischmann Foundation of Nevada, by grant CA-08748 from the National Cancer Institute, by grant 5 SO1 FR 05335-07 from the National Institutes of Health, by a grant from the National Cystic Fibrosis Research Foundation, and by an Institutional Grant to the School of Dental and Oral Surgery, Columbia University, from the National Institutes of Health.The authors are indebted to Dr.Louis Mandel for performing the biopsies used in this study. The expert technical assistance of Mrs.Mona Seggio is acknowledged. 相似文献
4.
We have investigated the extent to which modifications in the essential fatty acid content of mammalian cells can affect prostaglandin production. Swiss mouse 3T3 cells stimulated with the calcium ionophore A23187 produced 1.7 to 7 times more prostaglandin E(2) (PGE(2)) when the cultures were supplemented with linoleic acid. Increases in PGE(2) production as a result of linoleic acid supplementation occurred under all culture conditions except during the first 24 hr after attachment, when prostaglandin production was very high. Arachidonic acid supplementation produced a similar enhancement in the capacity of the cells to produce PGE(2), but no appreciable increase occurred when the cultures were supplemented with oleic acid. The phospholipids of the cells exposed to the linoleate-enriched medium contained 4 times more arachidonic acid and twice as much linoleic acid as compared with the corresponding controls. The choline phosphoglycerides were most highly enriched in arachidonic acid, but 2- to 3-fold increases also occurred in the inositol and ethanolamine phosphoglycerides. When cultures initially enriched with linoleic acid were transferred to an unsupplemented medium, the fatty acid composition as well as the capacity of the cells to produce PGE(2) reverted almost to control values. The amount of exogenous arachidonic acid converted to PGE(2) as measured by radioimmunoassay also was greater when the cells were enriched with linoleic acid. Studies with radioactive arachidonic acid indicated that the distribution of prostaglandin metabolites was not affected appreciably by linoleic acid enrichment. These findings suggest that at least two factors contribute to the increased capacity of the cultures supplemented with linoleate to produce PGE(2). One is enrichment of the phospholipid substrate pools with arachidonic acid. The other is an increased ability of the cells to synthesize PGE(2) from unesterified arachidonic acid, perhaps because the prostaglandin-forming enzymes are more active.-Denning, G. M., P. H. Figard, and A. A. Spector. Effect of fatty acid modification on prostaglandin production by cultured 3T3 cells. 相似文献
5.
Bradykinin stimulates Cl- secretion by airway epithelia, but different patterns of secretion result from addition to the mucosal and submucosal surfaces. Earlier work suggested that bradykinin activates two second messenger pathways: increasing inositol phosphates (InsP) via phosphatidylinositol bisphosphate hydrolysis and increasing cAMP via arachidonic acid metabolism. In this study, we measured arachidonic acid release and InsP production in cultured canine tracheal epithelial cells. Bradykinin increased the two second messengers via independent mechanisms: (a) dose-response curves with different incubation media demonstrated that each second messenger could be generated independently of the other; (b) phorbol ester inhibited InsP production but stimulated arachidonic acid release; (c) for polarized cultures, submucosal bradykinin stimulated production of both second messengers but mucosal bradykinin stimulated only arachidonic acid release. To determine if differences in second messenger formation at the two membranes resulted from differences in hormone-receptor interactions, we compared bradykinin binding to the apical and basolateral membranes. Both the binding capacities and affinity constants (KD) were different (basolateral KD, 257 +/- 53 pM; apical KD, 39 +/- 3 pM). These data demonstrate polarized coupling of bradykinin receptors to second messenger pathways in airway epithelial cells and suggest that this polarized coupling is due to different bradykinin receptors at the two membranes. 相似文献
6.
Retention of human skin fibroblast fatty acid modifications during maintenance culture 总被引:1,自引:0,他引:1
Arthur A. Spector Gerene M. Denning Lynn L. Stoll 《In vitro cellular & developmental biology. Plant》1980,16(11):932-940
Summary The fatty acid composition of cultured human skin fibroblasts was modified by adding either oleic or linoleic acid to the
growth medium. After the cultures became confluent, they were washed and transferred to different maintenance media in order
to determine the stability of the various fatty acyl modifications. Some changes in fatty acid composition occurred under
all conditions. When the maintenance medium was supplemented with fatty acid, the cellular neutral lipid and phospholipid
fatty acyl composition were altered markedly within 16 to 24 hr. If no supplemental fatty acid was available during the maintenance
period, however, the modified fatty acyl compositions were sufficiently retained so that appreciable differences between the
cells enriched with oleate and linoleate persisted for at least 48 to 72 hr. This considerable degree of stability occurred
when either 10% delipidized fetal bovine serum or 10% fetal bovine serum containing its inherent lipids were present in the
maintenance medium. Although the triglyceride content of the fatty acid-modified cells was quite labile, neither the cholesterol
nor phospholipid content changed appreciably during culture in any of the maintenance media. Since the fatty acid compositional
differences persisted during several days of maintenance under certain conditions, these modified cultures appear to be a
useful experimental system for assessing the effect of lipid structure on fairly long-term cellular functions.
This work was supported by Arteriosclerosis Specialized Center of Research Grant HL14230 from the National Heart, Lung and
Blood Institute, National Institutes of Health. 相似文献
7.
Andrew E. Schuh Thomas Lauvaux Tristram O. West A. Scott Denning Kenneth J. Davis Natasha Miles Scott Richardson Marek Uliasz Erandathie Lokupitiya Daniel Cooley Arlyn Andrews Stephen Ogle 《Global Change Biology》2013,19(5):1424-1439
An intensive regional research campaign was conducted by the North American Carbon Program (NACP) in 2007 to study the carbon cycle of the highly productive agricultural regions of the Midwestern United States. Forty‐five different associated projects were conducted across five US agencies over the course of nearly a decade involving hundreds of researchers. One of the primary objectives of the intensive campaign was to investigate the ability of atmospheric inversion techniques to use highly calibrated CO2 mixing ratio data to estimate CO2 flux over the major croplands of the United States by comparing the results to an inventory of CO2 fluxes. Statistics from densely monitored crop production, consisting primarily of corn and soybeans, provided the backbone of a well studied bottom‐up inventory flux estimate that was used to evaluate the atmospheric inversion results. Estimates were compared to the inventory from three different inversion systems, representing spatial scales varying from high resolution mesoscale (PSU), to continental (CSU) and global (CarbonTracker), coupled to different transport models and optimization techniques. The inversion‐based mean CO2‐C sink estimates were generally slightly larger, 8–20% for PSU, 10–20% for CSU, and 21% for CarbonTracker, but statistically indistinguishable, from the inventory estimate of 135 TgC. While the comparisons show that the MCI region‐wide C sink is robust across inversion system and spatial scale, only the continental and mesoscale inversions were able to reproduce the spatial patterns within the region. In general, the results demonstrate that inversions can recover CO2 fluxes at sub‐regional scales with a relatively high density of CO2 observations and adequate information on atmospheric transport in the region. 相似文献
8.
Nucleoporins with phenylalanine-glycine repeats (FG Nups) function at the nuclear pore complex (NPC) to facilitate nucleocytoplasmic transport. In Saccharomyces cerevisiae, each FG Nup contains a large natively unfolded domain that is punctuated by FG repeats. These FG repeats are surrounded by hydrophilic amino acids (AAs) common to disordered protein domains. Here we show that the FG domain of Nups from human, fly, worm, and other yeast species is also enriched in these disorder-associated AAs, indicating that structural disorder is a conserved feature of FG Nups and likely serves an important role in NPC function. Despite the conservation of AA composition, FG Nup sequences from different species show extensive divergence. A comparison of the AA substitution rates of proteins with syntenic orthologs in four Saccharomyces species revealed that FG Nups have evolved at twice the rate of average yeast proteins with most substitutions occurring in sequences between FG repeats. The rapid evolution of FG Nups is poorly explained by parameters known to influence AA substitution rate, such as protein expression level, interactivity, and essentiality; instead their rapid evolution may reflect an intrinsic permissiveness of natively unfolded structures to AA substitutions. The overall lack of AA sequence conservation in FG Nups is sharply contrasted by discrete stretches of conserved sequences. These conserved sequences highlight known karyopherin and nucleoporin binding sites as well as other uncharacterized sites that may have important structural and functional properties. 相似文献
9.
10.
O'Malley YQ Abdalla MY McCormick ML Reszka KJ Denning GM Britigan BE 《American journal of physiology. Lung cellular and molecular physiology》2003,284(2):L420-L430
The Pseudomonas aeruginosa secretory product pyocyanin damages lung epithelium, likely due to redox cycling of pyocyanin and resultant superoxide and H(2)O(2) generation. Subcellular site(s) of pyocyanin redox cycling and toxicity have not been well studied. Therefore, pyocyanin's effects on subcellular parameters in the A549 human type II alveolar epithelial cell line were examined. Confocal and electron microscopy studies suggested mitochondrial redox cycling of pyocyanin and extracellular H(2)O(2) release, respectively. Pyocyanin decreased mitochondrial and cytoplasmic aconitase activity, ATP levels, cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and mitochondrial membrane potential. These effects were transient at low pyocyanin concentrations and were linked to apparent cell-mediated metabolism of pyocyanin. Overexpression of MnSOD, but not CuZnSOD or catalase, protected cellular aconitase, but not ATP, from pyocyanin-mediated depletion. This suggests that loss of aconitase activity is not responsible for ATP depletion. How pyocyanin leads to ATP depletion, the mechanism of cellular metabolism of pyocyanin, and the impact of mitochondrial pyocyanin redox cycling on other cellular events are important areas for future study. 相似文献