Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gonococci do not cause genital infection in any convenient experimental animal, but all too easily cause genital infection in humans. To determine the 'evolutionary watershed' of gonococcal infections (the point on the evolutionary tree at which susceptibility to gonococcal infection begins) we extended previous studies of the interaction of gonococci with animal oviduct mucosa to include chimpanzees and baboons. Gonococci attached to, damaged, and invaded the oviduct (fallopian tube) mucosa of chimpanzees (which are apes) but not the oviduct mucosa of baboons (which are monkeys). Thus, the pattern of gonococcal infection in chimpanzees was identical to that in humans, whereas the pattern in baboons was like that in other animals. These studies indicate that the point in evolution at which susceptibility to gonococcal infection commences is between baboons and chimpanzees (or between monkeys and apes). Susceptibility to gonococcal disease appears to require the presence on genital epithelial cells of receptors for gonococcal ligands such as pili, receptors for gonococcal lipopolysaccharide, or both. The physiological role of these receptors may be to interact with more useful, as yet unidentified molecules.
 ...
PMID:The evolutionary watershed of susceptibility to gonococcal infection. 212 57

An experimental model using human fallopian tubes in organ culture was used to study the localization of purified gonococcal lipopolysaccharide (LPS). LPS was visualized by light microscopy with immunoperoxidase staining. Immediately after addition to fallopian tube organ cultures, gonococcal LPS aggregated on the tips of cilia. By 1 to 2 h after exposure, LPS could be seen distributed throughout the cytoplasm of ciliated and nonciliated cells in structures resembling vesicles. By 12 h, there were sloughed, ciliated cells present in the fallopian tube lumen, which had positive LPS stain on their surfaces as well as in their cytoplasm. By 24 h, LPS was distributed throughout the cytoplasm. Control experiments with rabbit oviduct organ cultures showed that LPS failed to attach, enter, or damage mucosal cells. These studies illustrate the initial localization of LPS on human mucosal cells and its uptake into the cells, which are coincident with toxicity for ciliated epithelial cells.
 ...
PMID:Localization of gonococcal lipopolysaccharide and its relationship to toxic damage in human fallopian tube mucosa. 241 54

We used an in vitro model of human nasopharyngeal tissue in organ culture to evaluate the effects of Neisseria meningitidis on human cilia and ciliary function. Encapsulated, viable meningococci damaged ciliated epithelium of nasopharyngeal organ cultures, whereas Neisseria subflava, a commensal species, did not. Meningococcus-induced ciliary damage was due to loss of ciliated cells to which meningococci were not attached. Damage was seen with piliated and nonpiliated meningococci and did not appear to require the presence of other specific meningococcal surface proteins. Meningococcal viability was a requirement for both ciliary damage and interactions of meningococci with microvilli of nonciliated epithelial cells. That is, filter-sterilized supernatants from meningococcus-infected organ cultures, heat-killed meningococci at high inoculum, and purified meningococcal or gonococcal lipopolysaccharide at concentrations of 100 micrograms/ml did not damage ciliary activity of nasopharyngeal organ cultures. In contrast, meningococcal lipopolysaccharide at 10 micrograms/ml markedly damaged ciliary activity of human fallopian tube organ cultures, suggesting a selective toxicity of lipopolysaccharide for specific human ciliated cells. Damage to nasopharyngeal ciliated epithelium by N. meningitidis may be an important first step in meningococcal colonization of the human nasopharynx, but meningococcal lipopolysaccharide does not appear to be directly responsible for this toxicity.
 ...
PMID:Analysis of damage to human ciliated nasopharyngeal epithelium by Neisseria meningitidis. 286 73

Despite the availability of effective antimicrobial agents and aggressive public health programmes, gonococcal infections, including salpingitis, remain a major worldwide problem resulting in significant rates of morbidity and infertility. Using an experimental model of gonococcal-infected human fallopian tubes in organ culture which are examined by light microscopy and scanning and transmission electron microscopy, basic pathogenic interactions between the gonococcus and the fallopian tube have been elucidated. The major steps in the pathogenic process include attachment, damage and invasion. Attachment appears to result from interaction of gonococcal pili with the tips of microvilli of non-ciliated cells of the fallopian tube mucosa. After gonococcal attachment occurs, fallopian tube damage is evident with loss of ciliary activity and sloughing of ciliated cells. The 2 compounds most likely to be mediators of this damage appear to be gonococcal lipopolysaccharide, which is released from the surface of the organism in the form of outer membrane blebs, as well as monomeric units of peptidoglycan, which are elaborated by the organism. Gonococcal attachment and perhaps elaboration of some molecule appear to initiate phagocytosis by non-ciliated epithelial cells. Gonococci are transported to the base of the non-ciliated cells and are released into the subepithelial space. This may lead to local disease (salpingitis) or disseminated disease (dermatitis-arthritis). Understanding the molecular mechanisms by which gonococci attach to, damage or invade the fallopian tube mucosa may result in identification of ways of preventing gonococcal infections and their sequelae.
 ...
PMID:Molecular mechanisms of pathogenicity of gonococcal salpingitis. 287 17

Studies of the interaction between Neisseria gonorrhoeae and human fallopian tube mucosa in organ culture suggest that attachment of gonococci is important, not only to secure th organism in the host, but also to initiate the disease process. The steps observed in gonococcal infection of fallopian tube organ cultures are: 1) attachment of gonococci to microvilli of nonciliated cells; 2) release from gonococci of lipopolysaccharide and possibly other toxic moities to cause mucosa damage; 3) engulfment or phagocytosis of gonococci by nonciliated cells; 4) transport of phagocytic vacuoles containing gonococci to the base of the nonciliated cells; and 5) exocytosis of gonococci within phagocytic vacuoles into the subepithelial tissues. In vivo, these steps might result in extensive local disease (e.g. salpingitis) or in the invasion of blood vessels to cause disseminated disease. Preliminary studies of human nasopharyngeal tissue in organ culture infected with Neisseria meningitidis indicate that meningococci attach to microvilli of nonciliated cells and are phagocytized by these cells. Meningococci subsequently appear in subepithelial tissues, though the route they take is not yet certain. These observations suggest at least some of the ways in which attachment may play a role in disease caused by N. gonorrhoeae and N. meningitidis. Mechanisms to block this attachment may provide new approaches to the prevention of infections caused by the pathogenic Neisseria.
 ...
PMID:Attachment of pathogenic Neisseria to human mucosal surfaces: role in pathogenesis. 612 78

An experimental model of human fallopian tubes in organ culture was used to examine the ability of lipopolysaccharide (LPS) of Neisseria gonorrhoeae to damage the fallopian tube mucosa. Gonococcal LPS was purified by hot phenol-water extraction and sequential ultracentrifugation. This LPS was highly lethal for lead-sensitized mice and at a concentration as low as 6 pg/ml reproducibly gelled limulus amoebocyte lysate. Gonococcal LPS damaged fallopian tube mucosa in concentrations as low as 0.015 microgram/ml, a values less than the LPS concentration in organ culture medium surrounding fallopian tube mucosa that was damaged by gonococcal infection. The toxic effect of LPS was neutralized by polymyxin B. Gonococci were shown to elaborate blebs of outer membrane material that is likely to contain LPS. These studies suggest that gonococci elaborate LPS-containing material into their surrounding medium, that the LPS is capable of mediating damage to human fallopian tube mucosa, and that the production of mucosal damage requires the lipid A portion of the LPS molecule.
 ...
PMID:Toxic activity of purified lipopolysaccharide of Neisseria gonorrhoeae for human fallopian tube mucosa. 678 65