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At least 19 recordsLinked to original sources
PubMed1991

Increase of T-cell receptor gamma/delta-bearing T cells in cord blood of newborn babies obtained by in vitro stimulation with mycobacterial cord factor.

Cord blood T lymphocytes proliferated in vitro in response to mycobacterial organisms but did not proliferate in the presence of tuberculin purified protein derivative. Components recognized by cord blood T cells were resistant to protease digestion. In contrast, T lymphocytes derived from tuberculin-positive adult peripheral blood proliferated when stimulated by the protease-sensitive component of mycobacterial organisms or purified protein derivative, confirming that adult T cells respond to protein components whereas cord blood T cells respond to the nonpeptide component of mycobacteria. In vitro culture of cord blood lymphocytes stimulated by either mycobacterial lysates or the lipid fraction showed increases in the numbers of T-cell receptor (TcR) gamma/delta T lymphocytes with no changes in the numbers of TcR alpha/beta T lymphocytes in contrast to the in vitro cultures of adult blood lymphocytes stimulated with mycobacterial ligands in which no increase of TcR gamma/delta cells was observed. Interleukin-2 receptor (CD25) and Ia antigen (HLA-DR) analyses evidenced the activation of a large proportion of cord blood gamma/delta T cells which had increased after stimulation with mycobacteria in vitro. Further characterization of mycobacterial ligand suggested that the lipid fraction of mycobacterial lysate or trehalose dimycolate-cord factor was the most plausible cause for T-cell proliferation in cord blood. These results suggest that when the gamma/delta T cells in a newborn infant not yet sensitized to any pathogenic organisms are confronted by a mycobacterium, they respond nonspecifically to the mycobacterial organism or its lipid component (cord factor). gamma/delta T cells may therefore play a distinct role in forming the first line of the host defense system against certain microorganisms.

Cord Factors↗
PubMed1978

Nonspecific immunostimulant activities of synthetic trehalose-6,6'-diesters (lower homologs of cord factor).

Mycobacterial cord factors (6,6'-diesters of trehalose with mycolic acids ranging from C80 to C90) have been shown to protect mice effectively against infection with Klebsiella pneumoniae or with Listeria monocytogenes. Our present findings indicate that the low-molecular-weight cord factor of Corynebacterium diphtheriae (with corynomycolic acids ranging from C28 PTO C36) is equally active. Moreover, its synthetic analog (with synthetic C32 mycolic acid) has the same activity. Two lower synthetic 6,6'-diesters of trehalose with C22 acids, which are described here for the first time, as well as dipalmitate and a dioleate of sucrose, were found inactive. The synthetic C76 trehalose diesters, which are capable of enhancing nonspecific resistance to infection, increase the immune response in mice, even when injected in metabolizable oil. They induce in the injected paws an inflammatory process weaker and more transient than the natural cord factor.

Adjuvants, Immunologic↗
PubMed1976

Adjuvant effect of cord factor, a mycobacterial lipid.

Cord factor was a good adjuvant in mice and rats but exerted little if any adjuvant effect in guinea pigs. In rats, cord factor not only enhanced antibody production but also induced delayed hypersensitivity. Wax D was a weak adjuvant in mice. Cord factor caused a marked inflammatory swelling at the sites of injection in mice, but it caused no such swelling in rats and guinea pigs.

Adjuvants, Immunologic↗
PubMed1980

Evidence for penetration in liposomes and in mitochondrial membranes of a fluorescent analogue of cord factor.

A fluorescent analogue of cord factor, a glycolipid toxin of mycobacteria, has been synthesized and its interactions with liposomes and isolated mitochondria have been studied. This compound, methyl alpha-D-6[12-(9-anthroyl)stearoyl]glucoside, is shown to be active against oxidative phosphorylation. When spread as a monolayer at the air-water interface, it forms a well organized phase and it strongly interacts with phosphatidylcholine. Addition of phosphatidylcholine liposomes or of isolated mitochondria to a water disperson of this fluorescent cord factor analogue results in a large increase of the fluorescence intensity. Moreover, the glycolipid probes for the temperature-dependent phase transition of the added suspensions. It is thus suggested that this cord factor analogue penetrates within mitochondrial membranes, a result which is discussed with respect to our previous conclusions concerning the way natural cord factors can interact with these organelles.

Animals↗
PubMed1979

A facile permethylation of cord factor.

Small quantities of cord factor (trehalose-6,6'-dimycolates) can be readily and almost quantitatively permethylated in anhydrous diethyl ether/dimethylformamide mixtures with CH3I and NaH-oil dispersion in the presence of molecular sieve. Hydrolysis of the permethylated products from cord factor "Peurois" and 'P3-Aoyama-b' prove these to be 6,6'-dimycolates. Experiments with a 4-palmitoyl glucose suggest that acyl migration in this system may not occur.

Chemical Phenomena↗
PubMed1988

Tumor necrosis factor (cachectin) mediates induction of cachexia by cord factor from mycobacteria.

The mechanism by which cord factor (CF), a toxic glycolipid from mycobacteria, induces cachexia was studied in BALB/c mice. Body weight was markedly reduced 48 h after CF administration; the animals became severely wasted and exhibited hypertriglyceridemia, hypoglycemia, and high levels of tumor necrosis factor (TNF) in plasma. After CF administration, a transferable factor which caused cachexia and hypertriglyceridemia in recipient mice was detected in the blood. Dexamethasone partially inhibited the cachexia-inducing action of CF. Conditioned medium from adherent peritoneal cell cultures incubated with CF produced the same wasting symptoms when inoculated intravenously into mice. These studies also demonstrated that adherent peritoneal cells produced a humoral factor in response to CF which was related to CF-induced cachexia. Antiserum to recombinant TNF-alpha prevented the cachectin action in passive-transfer experiments. Our findings indicate that cachectin (TNF) plays a role as a central mediator of the wasting induced by CF.

Animals↗
PubMed1995

Activation of protein kinase C by mycobacterial cord factor, trehalose 6-monomycolate, resulting in tumor necrosis factor-alpha release in mouse lung tissues.

Cord factors are mycoloyl glycolipids in cell walls of bacteria belonging to Actinomycetales, such as Mycobacterium, Nocardia and Rhodococcus. They induce granuloma formation in the lung and interstitial pneumonitis, associated with production of macrophage-derived cytokines. We studied how cord factors induce biological activities in the cells. Cord factors isolated from M. tuberculosis, trehalose 6-monomycolate (mTMM) and trehalose 6,6'-dimycolate (mTDM), enhanced protein kinase C (PKC) activation in the presence of phosphatidylserine (PtdSer), diacylglycerol and Ca2+, and mTMM activated PKC alpha more strongly than PKC beta or gamma under the same assay conditions. Kinetic studies of mTMM in response to PKC activation revealed that mTMM increased the apparent affinity of PKC to Ca2+ in the presence of both PtdSer and diolein. Although this is similar to observations with unsaturated fatty acids, such as arachidonic acid, mTMM was synergistic with PtdSer for PKC activation, but arachidonic acid was not. mTMM was also different as regards PKC activation, as phorbol ester was. A single i.p. administration of mTMM to mouse induced tumor necrosis factor-alpha (TNF-alpha) in serum and in the lung, which is a unique target tissue of cord factors. Based on our recent finding that TNF-alpha is an endogenous tumor promoter, the correlation between lung cancer and pulmonary tuberculosis is discussed.

Animals↗
PubMed1999

Production and partial characterization of anti-cord factor (trehalose-6,6'-dimycolate) IgG antibody in rabbits recognizing mycolic acid subclasses of Mycobacterium tuberculosis or Mycobacterium avium.

An ELISA with cord factor (trehalose-6,6'-dimycolate) is useful for the serodiagnosis of tuberculosis. To clarify the exact antigenic epitope in cord factor, recognized by a rabbit anti-cord factor IgG antibody, and to ascertain the most sensitive and specific diagnostic test antigen, rabbits were immunized with two kinds of cord factors isolated from Mycobacterium tuberculosis or Mycobacterium avium and the reactivities of the sera were tested against cord factors or the component mycolic acid methyl esters by ELISA. The serum from rabbits immunized with M. tuberculosis cord factor was highly reactive against M. tuberculosis cord factor, but less reactive against M. avium cord factor. In contrast, the serum from rabbits immunized with M. avium cord factor was highly reactive against M. avium cord factor but less reactive against M. tuberculosis cord factor. Moreover, the serum from rabbits immunized with M. tuberculosis cord factor reacted against mycolic acid methyl esters, especially methoxy mycolic acid methyl ester. On the other hand, the serum from rabbits immunized with M. tuberculosis cord factor was less reactive against trehalose-6-monomycolate and not reactive against sulfolipid (2,3,6,6'-tetraacyl trehalose 2'-sulfate). From these results, it was concluded that the anti-cord factor IgG antibody, produced experimentally in rabbits, recognized the differences in the cord factor structures, i.e. the hydrophobic moiety rather than the carbohydrate moiety. It was also noted that the serum from rabbits immunized with M. tuberculosis cord factor was highly reactive against methoxy mycolic acid as an epitope. This paper is the first to describe how the anti-cord factor IgG antibody can recognize the mycolic acid subclasses, which differ according to the species of mycobacteria.

Animals↗
PubMed1999

Anti-cord factor (trehalose 6,6'dimycolate) IgG antibody in tuberculosis patients recognizes mycolic acid subclasses.

The detection of anti-cord factor (trehalose 6,6'-dimycolate) IgG antibody in active (smear-and/or culture-positive) and inactive (smear-and culture-negative) tuberculosis patients is a useful serodiagnostic tool that can be used for early clinical diagnosis of the disease. We estimated the titers of anticord factor IgG antibody in the sera of tuberculosis patients, and compared them with those of Mycobacterium avium-infected patients. Most of the serum samples obtained from the tuberculosis patients were highly reactive against M. tuberculosis (MTB) cord factor isolated from M. tuberculosis H37Rv, a human-type mycobacterial strain, whereas they were less reactive against M. avium (MAC) cord factor. Similarly, most of the serum samples of the MAC-infected patients were highly reactive against MAC cord factor and less reactive against MTB cord factor. These results suggest that anti-cord factor IgG antibody recognizes the mycolic acid subclasses as an epitope which comprises cord factor, since MTB and MAC cord factor differ in mycolic acid subclasses and molecular species composition. To clarify the exact antigenic epitope in cord factor and to find out a more sensitive and specific diagnostic test antigen, we examined the reactivity of patients' sera to glycolipids containing trehalose (cord factor and sulfolipid) obtained from various mycobacterial species. Furthermore, the reactivity of human antisera to various mycolic acid subclasses (alpha-, methoxy and keto mycolic acids) of MTB cord factor was compared. We found that anti-cord factor IgG antibody in the sera of human tuberculosis patients most strikingly recognized methoxy mycolic acid in the cord factor of M. tuberculosis, whereas it recognized alpha- and keto mycolic acids weakly. Pre-absorption studies of antibody with MTB cord factor or methoxy mycolic acid methyl ester showed that anti-cord factor antibody was absorbed partially, but consistently. This is the first report describing that the specific subclass of mycolic acid from mycobacteria is antigenic in the humoral immune system of human tuberculosis infection.

Antibodies, Bacterial↗
PubMed1981

Proliferative responses of central and peripheral rat lymphocytes elicited by cord factor (trehalose 6,6'-dimycolate).

Cord factor--a mixture of 6,6'-diesters of alpha, alpha-D-trehalose with natural mycolic acids--which is purified from mycobacteria and other microorganisms, is known to have adjuvant activity as well as to enhance nonspecific resistance to infections and tumor development. In this work, trehalose 6,6'-dimycolate (TDM) was found to induce proliferative responses in rat thymus and lymph node cells. With the thymus cells, TDM responses were greater after removal of the adherent cell subpopulation. Consistent with this observation was the finding that addition of phagocytic cells purified from peritoneal or lymph node cell suspensions to nonadherent thymocytes abrogated the response of thymocytes to TDM. With the lymph node cells, the presence or removal of adherent cells had no major consequence on the TDM-induced proliferative response, since similar increases in deoxyribonucleic acid synthesis were observed with unfractionated and nonadherent cells. The difference between the sensitivities of thymus cells and lymph node cells to regulation by adherent cells indicated the existence of more than one type of TDM responder cell in rats. TDM also displayed marked stimulatory activity on thymus and lymph node cells from germ-free rats, ruling out the possibility that TDM might have triggered a specific, secondary, in vitro immune response. Expansion of a selected cell population(s) triggered by TDM may be involved in the manifestation of adjuvant activity and possibly other immunological properties of cord factor.

Animals↗
PubMed1977

Adjuvanticity (immunity-inducing property) of cord factor in mice and rats.

Cord factor, a glycolipid in mycobacteria, was found to make a tolerogenic protein antigen immunogenic when injected 0 to 2 days before tolerogen injection in mice and rats. Cord factor was also found to increase phagocytic function of the reticuloendothelial system of mice, and the relationship between the immunity-inducing capacity and the phagocytic function is discussed.

Adjuvants, Immunologic↗
PubMed1973

Granulomatous hypersensitivity to trehalose-6,6'-dimycolate (cord factor) in mice infected with BCG.

Cord factor in the form of emulsion is unable to sensitize mice to react with a more extensive granulomatous response to a subsequent challenge with the same substance. Mice infected with BCG bacilli are sensitized to cord factor. Such animals react to administration of cord factor with a very extensive granulomatous response, much stronger than normal ones. This hypersensitivity seems to be specific and is distinct from delayed hypersensitivity to PPD. PPD, administered to mice sensitized with BCG bacilli, has no effect on the granulomatous response. Our findings and their importance are discussed.

Animals↗
PubMed1972

Antibody formation to trehalose-6,6'-dimycolate (cord factor) of Mycobacterium tuberculosis.

A complex of trehalose-6, 6'-dimycolate (cord factor) and methylated bovine serum albumin was prepared, and its effect on the toxicity of cord factor in mice was studied. Either the active immunization with cord factor-methylated bovine serum albumin complex or the passive transfer of sera of rabbits vaccinated with the complex protected mice against the toxic action of cord factor. The antisera of mice and rabbits and gamma globulin fraction of rabbit antiserum demonstrated a precipitin reaction with an aqueous emulsion of cord factor. The reactivity of anticord factor was totally lost by treatment with 2-mercaptoethanol. The antigenic determinant group of cord factor was alpha-d-trehalose. Cord factor-anticord factor complex was devoid of activity to induce in vitro swelling and inhibition of respiratory and phosphorylative activity of mouse liver mitochondria. These results suggest that vaccination with cord factor-methylated bovine serum albumin complex induced the production of antibody to cord factor in mouse and rabbit serum which binds to cord factor and neutralizes its toxic activity either in vivo or in vitro.

Animals↗
PubMed1994

Interaction of cord factor (alpha, alpha'-trehalose-6,6'-dimycolate) with phospholipids.

We previously reported that cord factor (alpha,alpha'-trehalose-6,6'-dimycolate) isolated from Nocardia asteroides strain GUH-2 strongly inhibits fusion between unilamellar vesicles containing acidic phospholipid. We chose to study the effects of this molecule on liposome fusion since the presence of N. asteroides GUH-2 in the phagosomes of mouse macrophages had been shown to prevent phagosomal acidification and inhibit phagosome-lysosome fusion. A virtually non-virulent strain, N. asteroides 10905, does not prevent acidification or phagosome-lysosome fusion and, further, contains only trace amounts of cord factor. In the present paper, we have investigated the effects of cord factor on phospholipid bilayers that could be responsible for the inhibition of fusion. We show that cord factor increases molecular area, measured by isothermal compression of a monolayer film, in a mixed monolayer more than would be expected based in its individual contribution to molecular area. Cord factor, as well as other glycolipids investigated, increased the overall hydration of bilayers of dipalmitoylphosphatidylcholine by 50%, as estimated from the unfrozen water fraction measured by differential scanning calorimetry. The effect of calcium on this increased molecular area and headgroup hydration was measured by fluorescence anisotropy and FTIR spectroscopy of phosphatidylserine liposomes. Both techniques showed that cord factor, incorporated at 10 mol%, increased acyl chain disorder over controls in the presence of Ca2+. However, FTIR showed that cord factor did not prevent headgroup dehydration by the Ca2+. The other glycolipids tested did not prevent either the Ca(2+)-induced chain crystallization or headgroup dehydration of phosphatidylserine bilayers. These data point to a possible role of the bulky mycolic acids of cord factor in preventing Ca(2+)-induced fusion of liposomes containing acidic phospholipids.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1976

Effects of cord factor on liver lipid: accumulation triglycerides.

A single intraperitoneal injection of cord factor induced a remarkable increase in the amounts of triglycerides in liver. This effect was specific for cord factor among various lipid fractions of tuberclebacilli. Other lipid species of liver than triglycerides were not affected by cord factor injection. The accumulation of triglycerides became evident 16 to 24 hours after the cord factor injection and reached the maximum at 48 hours. As small a quantity as 12.5 mug of cord factor effectively induced the increase of triglycerides in liver.

Animals↗
PubMed1977

Enhancement of nonspecific immunity to bacterial infection by cord factor (6,6'-trehalose dimycolate).

The capacity of mycobacteria to enhance the nonspecific resistance of mice to bacterial infections was related to the presence of cord factor. After enzymatic digestion and delipidation, cell walls lost their immunopotentiating activity, which was restored, however, by the addition of cord factor. Cord factor administered alone protected mice effectively against virulent organisms unrelated to mycobacteria. Moreover, although this glycolipid is usually injected as a solution in mineral oil, our data show its effectiveness when administered in metabolizable peanut oil or even as a suspension in water. Since cord factor is a chemically well-defined molecule (6,6'-trehalose dimycolate), this glycolipid should constitute a new and useful tool for the investigation of nonspecific immunity to infection.

Animals↗