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1.
Analysis of the fine specificity and cross-reactivity of monoclonal anti-lipid A antibodies 总被引:3,自引:0,他引:3
T N Kirkland D E Colwell S M Michalek J R McGhee E J Ziegler 《Journal of immunology (Baltimore, Md. : 1950)》1986,137(11):3614-3619
We have investigated the fine specificity of anti-lipid A antibodies to identify conserved lipid A antigens. Because lipid A derived from many different Gram-negative bacteria has similar biologic activities, the conserved regions may be of particular importance for the immunostimulatory and toxic properties of lipid A. We found that five of nine antibodies bound to a wide variety of Gram-negative bacteria. All these widely cross-reactive antibodies bound to the same antigenic site within lipid A. Polymyxin B, an inhibitor of lipid A activity, bound to this site as well. The widely cross-reactive antibodies bound to native and base-hydrolyzed lipid A equally well, and also bound to the monosaccharide precursor lipid X. The less cross-reactive antibodies recognized base-hydrolyzed lipid A poorly, and did not recognize lipid X at all. Other investigators have shown that lipid X has some of the activities of lipid A in vitro and can inhibit the lethal toxicity of LPS in vivo. On the basis of this study, we suggest that lipid X contains a conserved lipid A epitope as well. 相似文献
2.
3.
Sami Ahmad Kenneth E. Kirkland Gary J. Blomquist 《Archives of insect biochemistry and physiology》1987,6(2):121-140
Direct evidence is presented for the role of a cytochrome P-450 monooxygenase (called mixed-function oxidase, or polysubstrate mono-oxygenase, PSMO) in the metabolism of the sex pheromone (Z)-9-tricosene to its corresponding epoxide and ketone in the housefly. A secondary alcohol, most likely an intermediate in the conversion of the alkene to the ketone, was also tentatively identified. The results of in vivo and in vitro experiments showed that the PSMO inhibitors, piperonyl butoxide (PB) and carbon monoxide, markedly inhibited the formation of epoxide and ketone from (9,10-3H) (Z)-9-tricosene. An examination of the relative rates of (Z)-9-tricosene metabolism showed that males exhibited a higher rate of metabolism than females with the antennae of males showing the highest activity of any tissue/organ examined. The major product from all tissues/organs was the epoxide. Data from experiments with subcellular fractions showed that the microsomal fraction had the majority of enzyme activity, which was strongly inhibited by PB and CO and required NADPH and O2 for activity. A carbon monoxide difference spectrum with reduced cytochrome showed maximal absorbance at 450 nm and allowed quantification of the cytochrome P-450 in the microsomal fraction of 0.410-nmol cytochrome P-450 mg?1 protein. Interaction of (Z)-9-tricosene with the cytochrome P-450 resulted in a type I spectrum, indicating that the pheromone binds to a hydrophobic site adjacent to the heme moiety of the oxidized cytochrome P-450. 相似文献
4.
J B Kirkland T M Bray W J Bettger 《Canadian journal of physiology and pharmacology》1987,65(8):1788-1792
The present study was designed to test the hypothesis that a pneumotoxin, 3-methylindole, alters the basic metabolic pathways involved in phospholipid and neutral lipid synthesis in cultured fibroblasts. Rat skin fibroblasts were obtained from day-old pups. Confluent monolayers were preincubated for up to 24 h with a range of concentrations (0-0.76 mM) of 3-methylindole. Following these treatments, the cell lipids were labelled by incubation for 6 h with [14C]glycerol. The lipids were extracted, separated by thin layer chromatography, and the radioactivity in each fraction was determined. 3-Methylindole had no effect on the total incorporation of [14C]glycerol into lipids, but significantly altered the distribution among lipid fractions. Incubation with 3-methylindole caused a decrease in the incorporation of [14C]glycerol into phosphatidylcholine, while radioactivity accumulated in the neutral lipid fraction. The other lipid fractions responded variably. Similarily, Flow 2000 human diploid lung fibroblasts were incubated for 24 h with 3-methylindole followed by treatment with [14C]glycerol, resulting in a 74% decrease in the incorporation of [14C]glycerol into phosphatidylcholine and a 50% increase in its accumulation in neutral lipid. The results indicate that 3-methylindole inhibits the synthesis of phosphatidylcholine from diacylglycerol precursors on the endoplasmic reticulum in cultured fibroblasts. This is an important observation as it shows that 3-methylindole affects the synthesis of phospholipids required for membrane turnover in cells that are not specialized for the production of phospholipids for surfactant. 相似文献
5.
Inhibition of lipopolysaccharide activation of 7OZ/3 cells by anti-lipopolysaccharide antibodies 总被引:2,自引:0,他引:2
T N Kirkland E J Ziegler P Tobias D C Ward S M Michalek J R McGhee I Macher K Urayama B J Appelmelk 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(9):3208-3213
We have investigated the ability of mAb against LPS to inhibit LPS-induced activation of 7OZ/3 pre-B cells. The fine specificity and relative affinity of these mAb for lipid A and LPS were also determined. We found that antibodies inhibited only the activity of glycolipids which they bound with relatively high affinity. However, two high affinity antibodies binding to non-lipid A epitopes did not block cellular activation. Some, but not all, relatively high affinity antibodies binding to the lipid A region of the LPS molecule inhibited biologic activity. The inhibitory antibodies bound to at least two distinct epitopes within the lipid A region. These data suggest that LPS interacts with 7OZ/3 cells in a highly specific fashion. 相似文献
6.
A 70,000-D membrane protein (MP70), which is restricted to the eye lens fibers and is present in immunologically homologous form in many vertebrate species, has been identified. By use of anti-MP70 monoclonal antibodies for immunofluorescence microscopy and electron microscopy, this polypeptide was localized in lens membrane junctional domains. Both immunofluorescence microscopy and SDS PAGE reveal an abundance of MP70 in the lens outer cortex that coincides with a high frequency of fiber gap junctions in the same region. 相似文献
7.
Intensity of photosynthesis and chlorophyll content as related to leaf age inNicotiana Sanderae hort
U r?zně starých list? v listové r??ici 90 a? 110 denních rostlin Nicotiana sanderae hort. byly sledovány rozdály v intensitě ?isté fotosynthesy a v obsahu chlorofylu (a + b). Ke stanovení intensity fotosynthesy bylo pou?ito dvou odli?ných metod, a to váhového stanovení p?ír?stku su?iny podle Barto?e, KubÍna a ?et-lÍka (1960) a gazometrického stanovení infra?erveným analyzátorem CO2. Nejvy??í intensitu fotosynthesy i nejvy??í obsah chlorofylu (vzhledem k plo?e listové) mají mladé, ale ji? dob?e rozvinuté listy, tj. t?etí a? ?tvrté od vrcholu (prvním listem se rozumí list o plo?e asi 20 cm2). Tyto listy nazýváme ?fotosyntheticky dospělými“. Listy nejmlad?í a zejména pak listy star?í mají intensitu fotosynthesy i obsah chlorofylu ni??í; u nejstar?ích list? je intensita fotosynthesy prakticky nulová. Intensita fotosynthesy i obsah chlorofylu se během vývoje mění: jejich momentální rozdíly u list? v genetické spirále jsou z?ejmě shodné s jejich změnami v ontogenesi listu. Pokles intensity fotosynthesy p?i stárnutí list? je rychlej?í ne? pokles obsahu chlorofylu. P?i ur?itém obsahu chlorofylu (tj. asi 2,25 a? 2,45 mg/dm2) klesá intensita ?isté fotosynthesy k nule. Intensita fotosynthesy je v lineárním vztahu k mno?ství chlorofylu (p?i p?epo?tu na plo?nou jednotku), a to nezávisle na poloze listu v genetické spirále. Obě pou?ité metody ke stanovení intensity fotosynthesy poskytly obdobné výsledky. 相似文献
8.
YOSHIKAZU NAKAMURA KIVOKATSU TANABE KOH.JI EGAWA 《The Journal of eukaryotic microbiology》1989,36(1):58S-60S
Pneumocystis carinii is a pathogen which, causes fatal pneumonia in patients with the acquired immune deficiency syndrome (AIDS). To facilitate the basic study of P. carinii , we have analyzed its major surface proteins by both immunochemical and biochemical methods. The major protein components of both cysts and trophozoites are a group of proteins called "P115" with apparent masses of 105–120 kd. It includes 6 isoelcclric variants. A monoclonal antibody raised against cysts recognizes all 6 variants and reacts with epitopes located in the cell wall indicating that P115 is an immunorcactive surface component. The isoelectric variants contain identical or closely related protein components and they are mannose-rich glycoproteins. The isoelectric variation may be due primarily to differences in glycosylation. The majority of sera from humans with diagnosed pneumocystosis that were tested reacted strongly with the P115 proteins. To develop probes for DNA diagnosis and to facilitate molecular studies, a genomic DNA library of P. carinii has been constructed. Some of these clones were used for DNA hybridization analysis of rat and human lungs. 相似文献
9.
溶液培养小麦幼苗转移至含Cd~(2 )的营养液中,根系乙烯产生较快地增加,约在12h达高峰,然后下降;ACC含量亦呈先升后降的趋势。未和Cd~(2 )溶液直接接触的地上部乙烯亦增加,至36h达高峰,此后急剧下降,而ACG和 MAGC含量持续上升。地上部乙烯的增加,主要是由通过根系运往地上部的镉直接作用的结果,不是根部合成ACG运往地上部后再产生的。电镜观察表明,地上部乙烯产生和ACC含量变化的时间进程,可以与镉进入叶细胞内的部位及其对细胞膜和细胞器的影响相联系。 相似文献
10.
I M Fearnley J E Walker R D Martinus R D Jolly K B Kirkland G J Shaw D N Palmer 《The Biochemical journal》1990,268(3):751-758
The ceroid lipofuscinoses are a group of neurodegenerative lysosomal storage diseases of children and animals that are recessively inherited. In diseased individuals fluorescent storage bodies accumulate in a wide variety of cells, including neurons. Previous studies of these bodies isolated from tissues of affected sheep confirmed that the storage occurs in lysosomes, and showed that the storage body is mostly made of a single protein with an apparent molecular mass of 3500 Da with an N-terminal amino acid sequence that is the same as residues 1-40 of the c-subunit (or dicyclohexylcarbodi-imide-reactive proteolipid) of mitochondrial ATP synthase. In the present work we have shown by direct analysis that the stored protein is identical in sequence with the entire c-subunit of mitochondrial ATP synthase, a very hydrophobic protein of 75 amino acid residues. As far as can be detected by the Edman degradation, the stored protein appears not to have been subject to any post-translational modification other than the correct removal of the mitochondrial import sequences that have been shown in other experiments to be present at the N-terminal of its two different precursors. No other protein accumulates in the storage bodies to any significant extent. Taken with studies of the cDNAs for the c-subunit in normal and diseased sheep, these results indicate that the material that is stored in lysosomes of diseased animals has probably entered mitochondria and has been subjected to the proteolytic processing that is associated with mitochondrial import. This implies that the defect that leads to the lysosomal accumulation concerns the degradative pathway of the c-subunit of ATP synthase. An alternative, but less likely, hypothesis is that for some unknown reason the precursors of subunit c are being directly mis-targeted to lysosomes, where they become processed to yield a protein identical with the protein that is normally found in the mitochondrial ATP synthase assembly, and which then accumulates. 相似文献