MediTest

Lipopolysaccharide endotoxin

Persistent chlamydial envelope antigens in antibiotic-exposed infected cells

Submitted by Jim K on Thu, 2005-09-15 22:32

J Infect Dis. 1999 Apr;179(4):954-66. 

 

Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis.

Wyrick PB, Knight ST, Paul TR, Rank RG, Barbier CS.

Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7290, USA. pbwyrick@med.unc.edu

An in vitro coculture model system was used to explore conditions that trigger neutrophil chemotaxis to Chlamydia trachomatis infected human epithelial cells (HEC-1B). Polarized HEC-1B monolayers growing on extracellular matrix (ECM) were infected with C. trachomatis serovar E. By 36 h, coincident with the secretion of chlamydial lipopolysaccharide and major outer membrane protein to the surfaces of infected cells, human polymorphonuclear neutrophils (PMNL) loaded with azithromycin migrated through the ECM and infiltrated the HEC-1B monolayer. Bioreactive azithromycin was delivered by the chemotactic PMNL to infected epithelial cells in concentrations sufficient to kill intracellular chlamydiae. However, residual chlamydial envelopes persisted for 4 weeks, and PMNL chemotaxis was triggered to epithelial cells containing residual envelopes. Infected endometrial cells demonstrated up-regulation of ENA-78 and GCP-2 chemokine mRNA. Thus, despite appropriate antimicrobial therapy, residual chlamydial envelope antigens may persist in infected tissues of culture-negative women and provide one source for sustained inflammation.<!--break-->

Persistent Chlamydial Enveolpe Antigens

Submitted by mrhodes40 on Mon, 2005-09-05 18:45

J Infect Dis. 1999 Apr;179(4):954-66.
†
Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis.
Wyrick PB, Knight ST, Paul TR, Rank RG, Barbier CS.
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7290, USA. pbwyrick@med.unc.edu
An in vitro coculture model system was used to explore conditions that trigger neutrophil chemotaxis to Chlamydia trachomatis infected human epithelial cells (HEC-1B). Polarized HEC-1B monolayers growing on extracellular matrix (ECM) were infected with C. trachomatis serovar E. By 36 h, coincident with the secretion of chlamydial lipopolysaccharide and major outer membrane protein to the surfaces of infected cells, human polymorphonuclear neutrophils (PMNL) loaded with azithromycin migrated through the ECM and infiltrated the HEC-1B monolayer. Bioreactive azithromycin was delivered by the chemotactic PMNL to infected epithelial cells in concentrations sufficient to kill intracellular chlamydiae. However, residual chlamydial envelopes persisted for 4 weeks, and PMNL chemotaxis was triggered to epithelial cells containing residual envelopes. Infected endometrial cells demonstrated up-regulation of ENA-78 and GCP-2 chemokine mRNA. Thus, despite appropriate antimicrobial therapy, residual chlamydial envelope antigens may persist in infected tissues of culture-negative women and provide one source for sustained inflammation.

Chemical, biological, and immunochemical properties of the Chlamydia psittaci lipopolysaccharide.

Submitted by Jim K on Wed, 2005-08-31 20:37

Infect Immun. 1986 Nov;54(2):568-74.

Brade L, Schramek S, Schade U, Brade H.
The lipopolysaccharide (LPS) of Chlamydia psittaci was extracted from yolk sac-grown elementary bodies, purified, and characterized chemically, immunochemically, and biologically. The LPS contained D-galactosamine, D-glucosamine, phosphorus, long-chain fatty acids, and 3-deoxy-D-manno-2-octulosonic acid in the molar ratio of approximately 1:2:2:6:5. The antigenic properties of the isolated LPS were compared with those of the LPS from Chlamydia trachomatis and Salmonella minnesota Re by the passive hemolysis and passive hemolysis inhibition tests, absorption, hydrolysis kinetics, and Western blot analysis with rabbit polyclonal antisera against chlamydiae and with a mouse monoclonal antibody recognizing a genus-specific epitope of chlamydial LPS. Two antigenic determinants were identified, one of which was chlamydia specific and the other of which was cross-reactive with Re LPS. Both determinants were destroyed during acid hydrolysis, whereby a third antigen specificity was exposed which was indistinguishable from the lipid A antigenicity. In rabbit polyclonal antisera prepared against Formalin-killed elementary bodies or detergent-solubilized membranes, two antibody specificities were differentiated. One of these was chlamydia specific, and the other was cross-reactive with Re LPS. The LPS of C. psittaci was inactive within typical endotoxin parameters (lethal toxicity, pyrogenicity, local Shwartzman reactivity); it was, however, active in some in vitro assays, such as those testing for mouse B-cell mitogenicity and the induction of prostaglandin E2 in mouse peritoneal macrophages.

Chlamydial lipopolysaccharide.

Submitted by Jim K on Wed, 2005-08-31 20:14

Biochim Biophys Acta. 1999 Oct 8;1455(2-3):387-402. Related Articles, Links

Chlamydial lipopolysaccharide.
Kosma P.
Universitat fur Bodenkultur Wien, Institute of Chemistry, Vienna, Austria. pkosma@edv2.boku.ac.at
Chlamydiae are obligatory intracellular parasites which are responsible for various acute and chronic diseases in animals and humans. The outer membrane of the chlamydial cell wall contains a truncated lipopolysaccharide (LPS) antigen, which harbors a group-specific epitope being composed of a trisaccharide of 3-deoxy-D-manno-oct-2-ulosonic (Kdo) residues of the sequence alpha-Kdo-(2-->8)-alpha-Kdo-(2-->4)-alpha-Kdo. The chemical structure was established using LPS of recombinant Escherichia coli and Salmonella enterica strains after transformation with a plasmid carrying the gene encoding the multifunctional chlamydial Kdo transferase. Oligosaccharides containing the Kdo region attached to the glucosamine backbone of the lipid A domain have been isolated or prepared by chemical synthesis, converted into neoglycoproteins and their antigenic properties with respect to the definition of cross-reactive and chlamydia-specific epitopes have been determined. The low endotoxic activity of chlamydial LPS is related to the unique structural features of the lipid A, which is highly hydrophobic due to the presence of unusual, long-chain fatty acids.

David Wheldon Comments on endotoxins & reactions

Submitted by Jim K on Sun, 2005-08-28 13:38

Cpn endotoxin is about 100 times less powerful than Neisserial endotoxin, but there must be a lot of it released, particularly with the active killing by metronidazole. Hence the need for caution at this stage of treatment. The long-term damaging effect of far more potent endotoxins on the CNS is vividly illustrated by this story: http://www.endotoxin.gmxhome.de/ which resulted in a letter in the BMJ: http://oem.bmjjournals.com/cgi/content/full/60/5/378

One quite common side effect of Cpn treatment is vestibular disturbance. A number of other medics who treat CFS with antibiotics have noticed this. It can go on for months, tends to have a diurnal rhythm and can be quite incapacitating. Its severity seems to be linked to bacterial load. The diurnal pattern suggests that it may be of host origin, perhaps cytokine. Here's a link to a webpage which notes the association between vestibular disturbance and cognitive deficits. http://www.backgroundfacts.com/menieres/COGDIS.htm

Cholesterol levels, bacterial endotoxin, and inflammation

Submitted by Jim K on Wed, 2005-08-24 20:24

Acute inflammation and infection maintain circulating phospholipid levels and enhance lipopolysaccharide binding to plasma lipoproteins
Richard L. Kitchens1,*, Patricia A. Thompson*, Robert S. Munford*, and Grant E. O'Keefe,**
* Departments of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9113
Microbiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9113
Surgery, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9113
** Department of Surgery, University of Washington, Harborview Medical Center, Seattle, WA 98104-2499

To whom correspondence should be addressed. e-mail: richard.kitchens@utsouthwestern.edu

Reactions to Treatment: Endotoxins, cytokines, porphyria, etc.

Submitted by Jim K on Mon, 2005-08-22 21:09

Bacterial Endotoxin reactions, Cytokine (immune) reactions and inflammation

These are often casually referred to as “herx” reactions, or scientifically as “herxheimer-like” alluding to the Jarisch-Herxheimer reaction to bacterial toxins specifically from syphilis. All gram-negative bacteria, of which Cpn is one, have contain Lipopolysaccharide endotoxin which is released as a matter of course during infection and is partially responsible for the on-going symptoms of the infection. When these bacterial are killed en masse they release larger amounts of endotoxin causing significant symptoms during initial phases of treatment. If the amount of endotoxin exceeds the body's ability to get rid of it, these toxic effects can be life threatening. Even in less threatening amounts, the endotoxins and the resulting reactions can cause oxidative stress and damage to body organs.