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1.
Resistance to human serum of gonococci in urethral exudates is reduced by neuraminidase 总被引:3,自引:0,他引:3
N J Parsons J A Cole H Smith 《Proceedings. Biological sciences / The Royal Society》1990,241(1300):3-5
Gonococci examined directly from urethral exudates are resistant to killing by human serum, but most strains become susceptible on subculture. Previous work with gonococci grown in vitro indicates that resistance in vivo is due to sialylation of gonococcal lipopolysaccharide (LPS) by a host factor, cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) or a related compound present in urogenital secretions and blood cells including phagocytes, which exude during inflammation. This sialylation inhibits the reaction between bactericidal IgM in serum and its target LPS sites. Here, we confirm the indication by using gonococci grown in vivo. Crucial to the above conclusions was the marked reduction of CMP-NANA-conferred serum resistance when gonococci were treated with neuraminidase to remove sialyl groups from their LPS. We now show that the serum resistance of gonococci in urethral exudates was reduced by treatment with neuraminidase from more than 95% (calculated in relation to controls incubated with heated serum) to 2-11% according to sample and incubation time. Subculture of the gonococci also reduced resistance to 9-11% but resistance was restored to more than 95% by incubation with CMP-NANA. This work is the culmination of an investigation that underlines the need to identify specific host factors and the virulence determinants they induce in vivo in future studies of pathogenicity. 相似文献
2.
Nicholas J. Parsons Alan Curry rew J. Fox Dennis M. Jones Jeffrey A. Cole Harry Smith 《FEMS microbiology letters》1992,90(3):295-299
Examined before subculture, gonococci in 18 urethral exudates collected from different patients were serum-resistant. For 15 exudates, the resistance was drastically reduced by treatment with neuraminidase and by one subculture on laboratory media. It was restored by incubation with cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA). Electron microscopic examination of gonococci in eight exudates showed a surface structure stained by Ruthenium red which disappeared in most samples when they were treated with neuraminidase. These results were identical with those of previous studies on in vitro grown gonococci which had shown that serum resistance is due to sialylation of a 4.5-kDa conserved component of gonococcal lipopolysaccharide (LPS) by host CMP-NANA, which masks the target site for bactericidal IgM and renders surface LPS stainable by Ruthenium red. The serum resistance of gonococci in the remaining three exudates was not reduced by neuraminidase nor by subculture. The mechanism of this stable resistance is unknown. 相似文献
3.
Lipopolysaccharide alteration is associated with induced resistance of Neisseria gonorrhoeae to killing by human serum 总被引:9,自引:0,他引:9
E L Tan P V Patel N J Parsons P M Martin H Smith 《Journal of general microbiology》1986,132(5):1407-1413
On SDS-PAGE, solubilized and proteinase K treated preparations of Neisseria gonorrhoeae strain BS4 (agar) showed differences in silver stained lipopolysaccharide (LPS) patterns, before and after induction to resistance to serum killing by incubation for 3 h at 37 degrees C with low Mr fractions from lysates of guinea pig red blood cells. Preparations from the original serum susceptible gonococci and LPS purified from such bacteria showed two components, but the preparations from the serum resistant gonococci were deficient in the higher Mr component. Furthermore, on immunoblotting with fresh human serum (FHS), the two LPS components of the susceptible gonococci reacted strongly with IgM. With preparations from the serum resistant gonococci there was no reaction in the area corresponding to the higher Mr component and a weaker reaction with the component of low Mr. Purified LPS from the susceptible gonococci neutralized the bactericidal activity of FHS against N. gonorrhoeae strain BS4 (agar) probably by reacting with the relevant antibody, since heated FHS was no longer bactericidal when mixed with a source of complement (human placental serum) after prior reaction with the LPS. These neutralization tests coupled with the results of immunoblotting strongly suggest that increased serum resistance is due to the lack of the high Mr LPS moiety. 相似文献
4.
Freshly isolated gonococci upon subculture are readily lysed by normal human serum although a few strains remain inherently resistant to the complement activity. The sensitive gonococci can be converted to serum resistance by incubation with a host derived factor referred to as cytidine 5-monophospho-N-acetylneuraminic acid (CMP-NANA). These gonococci resist complement mediated killing due to their sialylation of an epitope structure on a component of lipo-oligosaccharide (LOS). In the present study, the kinetics of conversion to serum resistance by the action of sialyltransferase (STase) inNeisseria gonorrhoeae was followed with very low concentrations of CMP-NANA. This conversion could not be perceived at 2×10–3 nmol.ml–1 but was fully attainable from 8×10–3 to 2×10–2 nmol.ml–1 CMP-NANA. When pretreated up to 100 min in presence of the very low concentration of 2×10–3 nmol.ml–1, a potentiating effect on the conversion of gonococci by 2×10–2 nmol.ml–1 was observed in relation to the time of preincubation. This action was abolished after exposure to a subinhibitory concentration of chloramphenicol (0.5 µg.ml–1). The gonococci recovered their ability to convert to serum resistance following adequate washing. The potential for increase in STase activity should be of interest for understanding the conversion from a serum sensitive to a serum resistance state. 相似文献
5.
The resistance of gonococci in most patients to complement mediated killing by human serum is due to sialylation of their lipopolysaccharide (LPS) which prevents bactericidal antibody from reacting with target sites. Two of the host factors responsible are: cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA), a well-known sialylating agent, and another factor which enhances the transfer of sialyl groups from CMP-NANA to LPS catalysed by a gonococcal sialyltransferase. The bacterial determinant of resistance is a conserved LPS component of about 4.5 kDa which is sialylated at a terminal Gal beta 1-4GlcNAc site on its side chain. The sialylated LPS forms a surface coat which is stainable by ruthenium red and connected with previously described 'capsules'. These observations sparked off an explosion of research. Recent publications show that sialylation of LPS by CMP-NANA affects additional important aspects of gonococcal pathogenicity, notably interactions with antibodies and phagocytes, and rendering the gonococcal surface more 'host-like'. Also, the observations have prompted an examination of LPS from some other pathogens for the presence of sialyl groups with positive results for Neisseria meningitidis and Haemophilus influenzae. 相似文献
6.
C A Nairn J A Cole P V Patel N J Parsons J E Fox H Smith 《Journal of general microbiology》1988,134(12):3295-3306
A low-Mr factor which induces gonococcal resistance to complement-mediated serum killing has been partially purified from lysates of mixed red and buffy coat cells from human blood. The lysates were dialysed against Tris buffer for 24 h at 25 degrees C with the diffusate being continuously recycled through a column of QAE-Sephadex A25. After elution in an NaCl gradient, the active fractions were both desalted and further purified on Sephadex G10. A second fractionation on QAE-Sephadex A25 and desalting with Sephadex G10 preceded further purification by repeated high-pressure liquid chromatography (HPLC) using a DEAE anion exchange column and desalting with Sephadex G10. Less than 500 micrograms of material showing one peak in HPLC was obtained from 1 litre of blood. After NMR had indicated the possible presence of pyrimidine nucleotide, carbohydrate and N-acetyl groups, nanogram quantities of a commercial preparation of cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) were shown to induce gonococci to serum resistance. The synthetic CMP-NANA also co-eluted with the preparation from blood cells in HPLC, and the two materials were indistinguishable in their patterns of acid and heat lability. Furthermore, the resistance-inducing activity of both materials was inhibited by cytidine monophosphate, which is known to inhibit sialylation reactions by CMP-NANA. It appears therefore that the resistance-inducing factor is CMP-NANA or a closely related compound. If the factor is CMP-NANA, biological activities indicated that the cell lysate from 1 litre of blood contained about 40 micrograms, and the most purified preparation contained only about 1%. With this minute amount in a mixture, the presence of CMP-NANA or a closely related analogue could not be established unequivocally by NMR. 相似文献
7.
Gonococci from subcutaneously implanted chambers in guinea pigs produced, on agar, more than 95% small colonies showing a "double highlight" (DH) effect in oblique reflected light combined with transmitted light. Laboratory strains of gonococci produced some DH colonies, but other showed a single highlight (SH) or no highlight (NH). Selection of DH colonies and comparison of their organisms with gonococci grown in vivo and with those from SH colonies, showed that the DH character was associated with high infectivity for guinea-pig chambers, resistance to killing by human phagocytes and heavy pilation. Furthermore, DH colonies were found in the first culture of three fresh samples of urethral pus. Thus, the DH colony characteristic may be a more reliable criterion of pathogenicity of gonococcal isolates than systems used previously. There were, however, some differences between the gonococci grown in vivo and the DH colony types. The gonococci grown in vivo and cultured once on solid medium possessed one or two antigens which differed from those of DH (or SH) colonies. They also formed smooth suspensions (which separated slowly) in saline, compared with the rough suspensions (which separated quickly) formed by gonococci from DH (or SH) colonies. Finally, the organisms grown in vivo were resistant to killing by human serum whereas the DH (and SH) colony types were susceptible; the resistance of the organisms grown in vivo was lost during one subculture on agar suggesting that the property is a phenotypic characteristic. Hence, in addition to selecting DH colony types the conditions in vivo produce organisms which differ, probably phenotypically, from cultured organisms. 相似文献
8.
M Goldner C W Penn S C Sanyal D R Veale H Smith 《Journal of general microbiology》1979,114(1):169-177
Some gonococci obtained from human urethral exudate or from subcutaneously implanted chambers in guinea pigs show a resistance to killing by human serum which is lost on sub-culture in vitro after a few generations. The environmental factors which may influence the phenotypic expression of resistance to serum killing were investigated in guinea pig chambers and in chamber fluid in vitro. The redox potential in chambers before and after infection was lower than that of heart blood but conditions were not anaerobic; H2O2 increased the redox potential but did not decrease gonococcal serum resistance. The chambers were slightly alkaline before and after infection. When the concentration of glucose (depleted in infected chambers by the abundant polymorphonuclear cells) was restored to excess, the serum resistance of the gonococci was unaffected. Concentrations of free amino acids in chambers changed little during infection. Gonococci adapted to growth in chambers and subsequently rendered serum-sensitive by growing once on agar reverted to serum-resistance after 0.5 to 1 h incubation in chamber fluid in vitro at 37 degrees C but not at 25 degrees C or 4 degrees C. After 16 to 24 h growth at 37 degrees C, resistance was again lost. The reversion to serum resistance did not occur in a complex laboratory medium. Examination of the chamber fluid after growth of gonococci in vitro showed depletion of lactate, glutamine and proline. 相似文献
9.
Alteration of pyocin-sensitivity pattern of Neisseria gonorrhoeae is associated with induced resistance to killing by human serum 总被引:3,自引:0,他引:3
F P Winstanley C C Blackwell E L Tan P V Patel N J Parsons P M Martin H Smith 《Journal of general microbiology》1984,130(5):1303-1306
A laboratory-grown strain of Neisseria gonorrhoeae, selected in vivo, BS4 (agar), is susceptible to complement-mediated killing by fresh human serum but is relatively resistant to killing by human phagocytes. It can be induced to serum resistance by incubation with a small molecular weight fraction of guinea pig serum. The serum-susceptible and induced-resistant forms show differences in pyocin sensitivity tests. This indicates either differences in the structure of their lipopolysaccharides or masking of some determinant(s). The pyocin sensitivity pattern of BS4 (agar) is only slightly different from that of a closely related strain, BSSH, which is more susceptible to killing by human phagocytes. 相似文献
10.
Protein changes associated with induced resistance of Neisseria gonorrhoeae to killing by human serum are relatively minor 总被引:2,自引:0,他引:2
P V Patel P M Martin E L Tan C A Nairn N J Parsons M Goldner H Smith 《Journal of general microbiology》1988,134(2):499-507
Serum-susceptible (SS) Neisseria gonorrhoeae were induced to resistance (SR) to complement-mediated killing by fresh human serum (FHS) by a small-Mr factor(s) from guinea-pig blood in 3 h at 37 degrees C, but not in the presence of bacteriostatic concentrations of chloramphenicol or neomycin, indicating that proteins mediated the acquisition of resistance. SDS-PAGE protein profiles of lysates of equal numbers of gonococci showed only two qualitative differences between SR and SS organisms, both in minor components (a protein A of about 205 kDa in the former and not the latter and vice versa for a protein B of about 16 kDa). Many proteins, however, including the three principal outer-membrane proteins, were present in larger amounts in SR gonococci. The lack of major changes in proteins when resistance is acquired was confirmed by immunoblotting the two protein profiles with the IgG of hyper-immune rabbit anti-SR and anti-SS sera, of rabbit anti-SR serum after absorption by SS organisms and of FHS used alone and after absorption with SS organisms. The IgM of FHS, which is responsible for most of the bactericidal activity, showed only faint reactions with a few proteins common to both SS and SR gonococci and no reactions when the FHS was absorbed with SS gonococci. This is in contrast to the strong and different reactions given with lipopolysaccharide (LPS) components of SS and SR organisms, which, prepared from the former organisms, neutralize the bactericidal activity of FHS. Hence, the relatively small protein changes accompanying induction are less likely to be directly responsible for serum resistance than the more profound LPS changes. 相似文献
11.
Physiology of sialic acid capsular polysaccharide synthesis in serogroup B Neisseria meningitidis 总被引:8,自引:4,他引:4
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The pathway for biosynthesis of sialic acid capsular polysaccharide was examined in Neisseria meningitidis serogroup B strain M986 and in strain PRM102, an isogenic mutant defective in polysaccharide production. Strain PRM102 was found to possess only 25% of the level of sialyltransferase activity that was found in strain M986, but it had wild-type levels of both the N-acetylneuraminic acid (NANA) condensing enzyme and the CMP-NANA synthetase. A new meningococcal enzyme, a CMP-NANA hydrolase, was found in both meningococcal strains. This enzyme generated CMP and NANA from CMP-NANA, had a Km of 0.88 microM, had a Vmax of 10.75 nmol of NANA produced per h per mg of protein, and was completely inhibited by 45.3 microM CMP. The sialyltransferase, which also had CMP-NANA as substrate, was insensitive to CMP addition. Subcellular fractionation and purification of cytoplasmic and outer membranes on sucrose density gradients revealed that both the sialyltransferase and the CMP-NANA hydrolase were cytoplasmic membrane associated. The NANA condensing enzyme and the CMP-NANA synthetase were found to be cytosolic. A working hypothesis for the regulation of sialic acid polysaccharide synthesis was developed. The CMP-NANA hydrolase with its high affinity for CMP-NANA regulates polysaccharide formation by the sialyltransferase, whereas CMP, a product of both the sialyltransferase and the CMP-NANA hydrolase, modulates the activity of the hydrolase on the cytoplasmic membrane. 相似文献
12.
Clay CD Soni S Gunn JS Schlesinger LS 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(8):5568-5578
The bacterium Francisella tularensis (Ft) is a potential weapon of bioterrorism when aerosolized. Macrophage infection is necessary for disease progression and efficient phagocytosis by human macrophages requires serum opsonization by complement. Microbial complement activation leads to surface deposition of a highly regulated protein complex resulting in opsonization or membrane lysis. The nature of complement component C3 deposition, i.e., C3b (opsonization and lysis) or C3bi (opsonization only) fragment deposition, is central to the outcome of activation. In this study, we examine the mechanisms of Ft resistance to complement-mediated lysis, C3 component deposition on the Ft surface, and complement activation. Upon incubation in fresh nonimmune human serum, Schu S4 (Ft subsp. tularensis), Fn (Ft subsp. novicida), and LVS (Ft subsp. holarctica live vaccine strain) were resistant to complement-mediated lysis, but LVSG and LVSR (LVS strains altered in surface carbohydrate structures) were susceptible. C3 deposition, however, occurred on all strains. Complement-susceptible strains had markedly increased C3 fragment deposition, including the persistent presence of C3b compared with C3bi, which indicates that C3b inactivation results in survival of complement-resistant strains. C1q, an essential component of the classical activation pathway, was necessary for lysis of complement-susceptible strains and optimal C3 deposition on all strains. Finally, use of Francisella LPS mutants confirmed O Ag as a major regulator of complement resistance. These data provide evidence that pathogenic Francisella activate complement, but are resistant to complement-mediated lysis in part due to limited C3 deposition, rapid conversion of surface-bound C3b to C3bi, and the presence of LPS O Ag. 相似文献
13.
Red blood cells, a source of factors which induce Neisseria gonorrhoeae to resistance to complement-mediated killing by human serum 总被引:5,自引:0,他引:5
P V Patel P M Martin M Goldner N J Parsons H Smith 《Journal of general microbiology》1984,130(11):2767-2770
Lysates of guinea pig or human red blood cells (RBC) contain far more of the factors that induce resistance in gonococci to complement-mediated killing by fresh human serum that do plasma or serum. As was previously found with serum, most of the resistance-inducing activity of guinea pig RBC lysates was found in ultrafiltrates with molecular weights of less than 5000. In contrast, and as with human serum, most of the resistance-inducing activity of human RBC lysates did not pass ultrafilters which removed molecules of less than 5000 daltons, although some active material of low molecular weight was present. 相似文献
14.
Schistosoma mansoni: killing of transformed schistosomula by the alternative pathway of human complement 总被引:2,自引:0,他引:2
The interaction of mechanically transformed schistosomula of Schistosoma mansoni with the alternative pathway of human complement was studied in vitro. To detect early changes in transformation, the schistosomula were prepared at a low temperature and used immediately. As shown previously, freshly transformed schistosomula were highly susceptible to killing by normal human serum and by C4-depleted normal human serum. This serum activity was concentration dependent and was markedly reduced on a twofold serum dilution. Upon incubation at 37 C in defined synthetic medium, schistosomula rapidly became refractory to killing by the alternative pathway of complement. After 1 hr of incubation at 37 C, the percentage of schistosomula which were resistant to killing increased from 16 to 85. This conversion was accompanied by a fivefold decrease in deposition of C3b on schistosomula which had been exposed to 37 C for 1 hr and then further incubated with C4-depleted normal human serum. The following events occurred concomitantly during incubation of freshly transformed schistosomula at 37 C with a half-life of 30-60 min: (1) Decrease in activation and consumption of the alternative pathway of complement by schistosomula; (2) appearance of a strong complement consuming activity in the supernatant of incubating schistosomula; and (3) shedding of protein- and carbohydrate-containing substances from the surface of schistosomula into the supernatant. Isolated external membranes of freshly transformed schistosomula consumed the alternative pathway of complement to a greater extent than membranes of schistosomula preincubated in medium at 37 C. The results demonstrate that transformed schistosomula acquire resistance to complement killing via the alternative pathway by shedding complement-activating substances.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
15.
N. J. Parsons P. V. Patel P. M. V. Martin E. L. Tan C. A. Nairn M. Goldner K. A. Brogden H. Smith 《Antonie van Leeuwenhoek》1987,53(6):551-555
A small M, heat and acid labile, host inducer(s) of gonococcal resistance to complement mediated killing by fresh human serum (-FHS), being purified from red blood cell (RBC) extracts, produced changed in lipopolysaccharide (LPS) structure, surface antigens and proteins; and acquirement of resistance related to loss of a target antigen for bactericidal IgM, possibly LPS components. A 20 kDalt, lipoprotein with a high content of glutamic acid isolated from outer membranes of a gonococcal strain selected in vivo is a determinant of gonococcal resistance to killing by human phagocytes. Somic extracts of gonococci may contain a cytotoxin for human phagocytes.At the 4th International Pathogenic Neisseriae Conference, we reported (Parsons et al. 1985) that conditions in vivo induced phenotypic change leading to gonococcal resistance to complement-mediated killing by human serum; and, also, selected gonococcal types which showed a greater resistance to intracellular killing by human phagocytes than laboratory strains. Furthermore, evidence was presented that not only was resistance to complement mediated killing important in gonococcal pathogenesis, but also resistance to phagocytic defences. This paper describes the continuance of our studies on the determinants of induced serum resistance and of resistance to killing by phagocytes including toxicity to these cells. Each section begins by summarising previous work that was referenced in Parsons et al. (1985). 相似文献
16.
Human factor H interacts selectively with Neisseria gonorrhoeae and results in species-specific complement evasion 总被引:1,自引:0,他引:1
Ngampasutadol J Ram S Gulati S Agarwal S Li C Visintin A Monks B Madico G Rice PA 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(5):3426-3435
Complement forms a key arm of innate immune defenses against gonococcal infection. Sialylation of gonococcal lipo-oligosaccharide, or expression of porin 1A (Por1A) protein, enables Neisseria gonorrhoeae to bind the alternative pathway complement inhibitor, factor H (fH), and evade killing by human complement. Using recombinant fH fragment-murine Fc fusion proteins, we localized two N. gonorrhoeae Por1A-binding regions in fH: one in complement control protein domain 6, the other in complement control proteins 18-20. The latter is similar to that reported previously for sialylated Por1B gonococci. Upon incubation with human serum, Por1A and sialylated Por1B strains bound full-length human fH (HufH) and fH-related protein 1. In addition, Por1A strains bound fH-like protein 1 weakly. Only HufH, but not fH from other primates, bound directly to gonococci. Consistent with direct HufH binding, unsialylated Por1A gonococci resisted killing only by human complement, but not complement from other primates, rodents or lagomorphs; adding HufH to these heterologous sera restored serum resistance. Lipo-oligosaccharide sialylation of N. gonorrhoeae resulted in classical pathway regulation as evidenced by decreased C4 binding in human, chimpanzee, and rhesus serum but was accompanied by serum resistance only in human and chimpanzee serum. Direct-binding specificity of HufH only to gonococci that prevents serum killing is restricted to humans and may in part explain species-specific restriction of natural gonococcal infection. Our findings may help to improve animal models for gonorrhea while also having implications in the choice of complement sources to evaluate neisserial vaccine candidates. 相似文献
17.
Monovalent rabbit antisera were prepared to highly purified gonococcal lipopolysaccharide (LPS), to pili and to two major purified outer envelope proteins. All these antisera were free from significant specific IgM antibody and were standardized to 4 microgram specific IgG antibody per test, permitting accurate comparisons between the different gonococcal surface antigens as triggers of the complement-dependent bactericidal reaction. LPS was the most effective antigen at inducing a bactericidal response to homologous and heterologous gonococci, followed by the two individual outer envelope proteins. Pili were relatively ineffective. Strain P9 gonococci grown in vivo or which possessed a 'capsule' in vitro were more resistant to serum killing than the non-capsulated parent strain. One highly susceptible strain, F62, which was killed by complement in the absence of any LPS antibody, was able to directly activate complement by the alternative pathway. 相似文献
18.
P. J. Hitchcock J. Boslego K. A. Joiner E. N. Robinson Jr 《Antonie van Leeuwenhoek》1987,53(6):509-518
The immunoaccessibility of the H8 antigen was examined as was the functionality of H8 specific monoclonal antibody (McAb 10). Immunoaccessibility of H8 varied among individual gonococci grown in vitro; the overall degree of variability was strain dependent. The H8 antigen was detected on the surface of most but not all gonococci found in urine sediment from an infected volunteer. The H8 specific McAb 10 was not bactericidal for strains of serum resistant gonococci; in the serum sensitive strain, an increase of approximately .5 logs above the bactericidal activity of antibody depleted normal human serum was observed. It is possible that the apparent paradox of the common, immunogenic, antigenic surface constituent H8 may be resolved in part by variation in immunoaccessibility within and among gonococcal strains. 相似文献
19.
M Panneerselvam S Welt L J Old C W Vogel 《Journal of immunology (Baltimore, Md. : 1950)》1986,136(7):2534-2541
The susceptibility of human melanoma cells to lysis by human complement after sensitization with the R24 murine IgG3 monoclonal antibody to the GD3 ganglioside antigen was investigated. It was found that the melanoma cell lines were either susceptible (greater than or equal to 70% cytotoxicity) or resistant (less than or equal to 30% cytotoxicity) to complement-mediated killing. We determined the kinetics of binding of C3 to and its subsequent fate on the melanoma cells. We found that on susceptible cell lines, maximal binding of C3 occurred within 10 min of incubation. At that time, approximately 90% of the bound C3 was in the form of C3b. During the subsequent incubation, the C3b was slowly inactivated, apparently generating the physiologic degradation products iC3b, C3dg, and C3d. However, this degradation of C3b could be inhibited without affecting the final degree of cytotoxicity, indicating that it is of no apparent consequence for the killing of susceptible melanoma cells. Very different results were obtained with resistant melanoma cells. Bound C3b was rapidly inactivated, and C3d was the predominant form of C3 on resistant cells throughout the incubation. Therefore, rapid inactivation of C3b was identified as a protective mechanism of human melanoma cells against complement attack. In addition, we found that resistance to complement is not an inherent property of the cells but depends on the antibody used for sensitization, because the resistant cell lines could be lysed after sensitization with polyclonal antiserum. 相似文献
20.
Antibodies to N-terminal peptides of gonococcal porin are bactericidal when gonococcal lipopolysaccharide is not sialylated 总被引:23,自引:0,他引:23
Christopher Elkins Nicholas H. Carbonetti Victor A. Varela Derek Stirewalt David G. Klapper P. Frederick Sparling 《Molecular microbiology》1992,6(18):2617-2628
Six synthetic 25-mer peptides corresponding to certain presumed surface-exposed regions of gonococcal porin protein I (PI) were made from strains FA19 (PIA) and MS11 (PIB). Four peptides were immunogenic in rabbits. Affinity-purified antisera against both PIA and PIB N-terminal peptides were bactericidal for homologous gonococci and many heterologous PI serovars. However, sialylation of gonococcal lipopolysaccharide (LPS) by growth of gonococci in the presence of cytidine monophosphate-neuraminic acid (CMP-NANA) abrogated the bactericidal activity of these antisera. Binding of anti-PI monoclonal antibodies to whole gonococci was reduced two- to fourfold by sialylation of LPS, suggesting that sialylation may inhibit bactericidal activity by masking porin epitopes. However, binding of anti-PII (Opa) monoclonal antibodies was not inhibited, yet complement-mediated killing was inhibited by sialylated LPS. Binding of complement components C3 and C9 was inhibited in the presence of either anti-PI or anti-PII monoclonals when gonococci were grown in the presence of CMP-NANA. Thus sialylation inhibited both anti-PI antibody binding and complement deposition, with a resultant decrease in bactericidal activity. 相似文献