Anti-inflammatory capacities of human milk: lactoferrin and secretory IgA inhibit endotoxin-induced cytokine release.
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Adenocarcinoma↗
Biomedical subjects
I Mattsby-Baltzer
Publications and source records attributed to I Mattsby-Baltzer.
Breast feeding: overview and breast milk immunology.
The transfer of host defence capacity to the human offspring provides a remarkable model of passive transfer of immunity. In fact it may also provide an example of active immunization. The transfer of mucosal protection via breast feeding offers many additional advantages for the mother and infant. Through its contraceptive effects it increases the spacing between births, thus diminshing the infant mortality and the burden on the mother. It also enhances bonding between mother and child, it seems to increase the IQ and school result of the infant and might decrease the risk of certain malignancies and perhaps of juvenile diabetes. A fully breast-fed infant receives as much as 0.5-1 g of secretory immunoglobulin A (SIgA) antibodies daily, the predominant antibody of human milk. This can be compared to the production of some 2.5 g of SIgA per day for a 60 kg adult. These SIgA antibodies have been shown to protect against Vibrio cholerae, ETEC, Campylobacter, Shigella and Giardia. Furthermore, milk is rich in receptor analogues for certain epithelial structures which microbes need for attachment to host tissues as an initial step in infections. Thus the adherence of Haemophilus influenzae and pneumococci for example to retropharyngeal cells is efficiently inhibited by human milk. This may be one explanation for the fact that breast-fed babies have less otitis media than the non-breast-fed. Other milk factors like lysozyme and lactoferin may contribute to the host defence, but this has not yet been well defined. However, human milk also supports the well-being of the infant by being anti-inflammatory.(ABSTRACT TRUNCATED AT 250 WORDS)
Breast Feeding↗
Endotoxin levels in sera of elderly individuals.
The endotoxin levels in serum of 377 72-year-old individuals were quantitated. The study population was a representative sample of this age group and was participating in a general study of health and disease among the elderly in Göteborg, Sweden. The endotoxin levels in serum were quantified by the chromogenic Limulus amebocyte lysate assay and were correlated with the health status and laboratory findings for each individual. The mean endotoxin levels (+/- 1 standard deviation) in men and women, when excluding four outliers, were 6.6 +/- 3.8 and 6.9 +/- 3.8 pg/ml, respectively. All included, 21.5% of individuals had endotoxin levels equal to or above the sensitivity limit of 10 pg/ml. Strong positive correlations were found between endotoxin levels and plasma triglycerides (P > 0.995) and between endotoxin levels and serum protein (P > 0.9875). The endotoxin activity also correlated with mean corpuscular hemoglobin concentration (P < 0.005, negative correlation), body mass index (P > 0.9875), and decreased appetite (P > 0.9875). A high alcohol consumption was associated with increased endotoxin levels (P = 0.995). There are no previous studies which examine endotoxin levels in serum samples from individuals representative of the population. This study showed that elderly individuals had the same mean level of endotoxin as has been found in other age groups. The increased endotoxin levels seen in heavy drinkers may be explained by a decreased ability of the liver to remove endotoxin. The correlations found between endotoxin and triglycerides, protein, mean corpuscular hemoglobin concentration, decreased appetite, and body mass index are discussed.
Aged↗
Endotoxin is angiogenic.
The formation of new blood vessels, angiogenesis, is an important event in inflammation, wound healing and tumour growth. Mediators produced by various cells when exposed to endotoxin include cytokines (tumour necrosis factor, interleukins 1 and 6, and basic fibroblast growth factor) which, it has been suggested, stimulate angiogenesis. The angiogenic effect of endotoxin (lipopolysaccharide, LPS) was studied in rats using the quantitative mesenteric window assay. Adult rats were injected intraperitoneally with Escherichia coli LPS (5 pg/ml-20,000 ng/ml) twice daily for 4.5 consecutive days and were sacrificed 14 days after the start of this treatment. An angiogenic response was observed at concentrations of > 2 ng/ml in a dose-dependent manner. No inflammatory cellular exudate was seen in the test tissue at the time of angiogenesis analysis. Suppressed body-weight gain, a marker of the systemic effect of LPS in the rat, was significant only at the highest dose tested. The data suggest that endotoxin-mediated neovascularization could be a component of inflammation and wound healing.
Animals↗
Endotoxin and interleukin-1 alpha in the cervical mucus and vaginal fluid of pregnant women with bacterial vaginosis.
OBJECTIVE: The purpose of our study was to determine the concentrations of endotoxin and interleukin-1 alpha in the cervical mucus and vaginal fluid of pregnant women who either did or did not have bacterial vaginosis. STUDY DESIGN: Samples of cervical mucus and vaginal fluid were collected from women in early pregnancy who had signs of bacterial vaginosis and from healthy control subjects. The samples were analyzed for the concentrations of endotoxin and interleukin-1 alpha. In addition, wet mounts were examined for signs of inflammation indicated by increased numbers of leukocytes. RESULTS: Both endotoxin and interleukin-1 alpha occurred in much higher concentrations (p < 0.0001, p < 0.0002) in both the cervical mucus and the vaginal fluid of women with signs of bacterial vaginosis than they did in healthy control subjects. A correlation was found between the interleukin-1 alpha concentrations in the vaginal fluid and the number of leukocytes as judged by a semi-quantitative evaluation of wet mounts (p = 0.0365). The concentrations of endotoxin correlated with those of interleukin-1 alpha in both fluids (vaginal fluid, p < 0.01; cervical mucus, p < 0.01). CONCLUSION: Our study shows that concentrations of endotoxin and interleukin-1 alpha in cervical mucus and vaginal fluid of women in early pregnancy who have bacterial vaginosis are significantly higher than the corresponding levels in control subjects.
Body Fluids↗
Lipid A in Helicobacter pylori.
Free lipid A of Helicobacter pylori was characterized with regard to chemical composition, reactivity with anti-lipid A antibodies, and activity in a Limulus lysate assay. The predominant fatty acids of H. pylori lipid A were 3-OH-18:0, 18:0, 3-OH-16:0, 16:0, and 14:0. Hexosamine was present in amounts similar to those in Campylobacter jejuni or Salmonella typhimurium lipid A. The lipopolysaccharide of H. pylori contained 2-keto-3-deoxyoctonic acid, a common constituent of enterobacterial and C. jejuni lipopolysaccharides. In the enzyme-linked immunosorbent assay, the doses of lipid A required to inhibit anti-lipid A by 50% (EI50 values) by absorption of the immune (rabbit) serum were 7.9, 1.2, and 1.4 micrograms of O-deacylated lipid A's from H. pylori, C. jejuni, and S. typhimurium per ml, respectively. The lower reactivity of H. pylori lipid A compared with those of the other two lipid A preparations (as shown by the higher EI50 value) was underscored by the use of a murine monoclonal anti-lipid A antibody in the inhibition assay. An EI50 value was not obtained at the concentrations tested for H. pylori lipid A; the corresponding figures for C. jejuni and S. typhimurium lipid A's were 13 and 14 micrograms/ml, respectively. No inhibition was obtained with H. pylori lipopolysaccharide, which showed a low-molecular-weight profile on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The activity of H. pylori lipid A in the Limulus assay was approximately 71 and 650 times lower than those of C. jejuni and S. typhimurium lipid A's, respectively. These findings suggest that lipid A is an integral part of the outer cell wall of H. pylori. The lower reactivity of H. pylori lipid A with anti-lipid A antibodies and in the Limulus assay compared with that of C. jejuni or S. typhimurium lipid A may be explained by a different composition of the fatty acids, especially the 3-hydroxy fatty acids, and a possible deviating phosphorylation pattern.
Animals↗
Adhesion-dependent activation of mucosal interleukin-6 production.
Mucosal exposure to Escherichia coli elicits an inflammatory response in the urinary tract. Interleukin-6 (IL-6) is secreted into the urine, and polymorphonuclear leukocytes (PMNLs) are recruited to the site of infection. This study analyzed the ability of mucosally administered bacterial components to activate IL-6 and PMNL responses. P, S, and type 1 fimbrial preparations with adhesins specific for Gal alpha 1-4Gal beta, NeuAc alpha 2-3Gal, and mannose, respectively, were inoculated intravesically into lipopolysaccharide (LPS)-responder (C3H/HeN) and LPS-nonresponder (C3H/HeJ) mice. The role of the fimbrial adhesin was examined by comparing P and S fimbriae with (Adh+) and without (Adh-) the receptor-binding domain. Isolated lipid A was used in parallel. The urinary IL-6 levels were elevated after challenge with Adh+ P fimbriae, but not after challenge with the Adh- P fimbriae, Adh+ or Adh- S fimbriae, or type 1 fimbriae. The activation was not a function of contaminating LPS, since it occurred in both LPS-responder and -nonresponder mice and since isolated lipid A was a poor activator of the IL-6 response. In contrast, lipid A was a potent inducer of the PMNL response. The results suggested that the IL-6 and PMNL responses were activated via different pathways; the IL-6 response was activated mainly by an adhesion-dependent interaction with the mucosa, and the PMNLs were activated mainly by lipid A. The results emphasize the active role of the mucosal barrier in the production of mediators in response to diverse bacterial stimulants.
Animals↗
Endotoxin shedding by enterobacteria: free and cell-bound endotoxin differ in Limulus activity.
The endotoxin activities of gram-negative bacteria and their lipopolysaccharides (LPS) have been quantitated by a chromogenic Limulus amocbocyte lysate (CLAL) assay. When bacterial cell exposing various cell surface structures were compared, the highest Limulus activities were found in R strains of Escherichia coli and Salmonella typhimurium mutants. E. coli with K antigens did not differ from K-negative strains. By measuring beta-hydroxymyristic acid (3-OH tetradecanoic acid, beta-OHC14:0), it was possible to compare the CLAL activities of LPS bound to bacterial cells, LPS shed into the culture medium, and purified LPS. After 16 h of growth, the cell-free culture supernatants of three E. coli O1K1 strains and S. typhimurium showed CLAL activities 14.3 to 20.3 times higher than did the corresponding bacterial cell suspensions in relation to their beta-OHC14:0 contents. Four other E. coli strains (O serotypes O14, O24, and O75) and the S. typhimurium 395 R mutants MR5 and MR6 showed CLAL values 2.8 to 7.9 times higher in their culture supernatants. LPS of E. coli O1K1 and S. typhimurium had lower CLAL activities than the culture supernatants (1/10 and 1/4, respectively). Although the beta-OHC14:0 concentrations of the culture supernatants were approximately half those of the corresponding bacterial cells, all had CLAL values that were 2 to 21 times higher. The bacterial cell suspension, culture supernatant, and purified LPS of S. typhimurium MS were compared by CLAL assay and a quantitative enzyme-linked immunosorbent assay based on monoclonal antibodies to the O5 antigen. Endotoxin shed into the culture medium was the most CLAL-active form of LPS, while purified LPS was the most antigen-active form. The results emphasize the importance of appropriate standards when quantifying endotoxin in various states. In conclusion, E. coli and S. typhimurium bacteria shed significant amounts of endotoxin into the surrounding medium during growth. This form of LPS is more CLAL active than the cell-bound or purified LPS.
Animals↗
Subclass distribution of IgG and IgA antibody response to Pseudomonas pseudoalcaligenes in humans exposed to infected metal-working fluid.
The subclass distribution of the IgG and IgA antibody response in serum was studied in humans exposed to aerosolized metal-working fluid containing Pseudomonas pseudoalcaligenes. This species was consistently found in concentrations of 10(8) bacteria per milliliter of metal-working fluid during 1 year of observation. No increased frequency of respiratory infections or discomfort was related to the exposure to the infected fluid. The antibody response to the bacterium consisted predominantly of IgG1 and IgG2 antibodies. IgG2 antibodies dominated the antibody response to the lipopolysaccharide of the bacterium. IgA1 and IgA2 antibodies were also found. Smokers had significantly reduced antibody levels of all subclasses compared with nonsmokers. The antibody levels in smokers did not differ from levels of the unexposed control group. Analyses of the total serum immunoglobulin concentrations with respect to subclasses revealed that the total IgG2 levels were also significantly reduced in smokers. In nonsmokers, the age of the individuals influenced the antibody levels of the IgG1, IgG2, IgA1, and IgA2 subclasses, the levels decreasing with increasing age. For smokers, the correlation between age and antibody levels was only obvious for IgG2 antibodies. Decreased IgG2 antibody levels in the smokers were also accompanied by decreased FEV1 values (p less than 0.01). Subclass analysis of the antibody response to P. pseudoalcaligenes demonstrated that the subclass pattern for the whole bacterium differed from the pattern of the major cell wall component, the lipopolysaccharide. The significance of qualitative and quantitative differences in the subclass antibody response is discussed.
Adult↗
Microbial growth and accumulation in industrial metal-working fluids.
The dynamics of microbial growth in metal-working fluids (MWF) and the effect of the addition of biocides were studied in large fluid systems, in this case, one central tank which holds 150 m3. In this system, populations of Pseudomonas pseudoalcaligenes (greater than 10(8) CFU/ml) were sustained for a year, although large quantities of biocides were added. Quantitation of 3-OH lauric acid, a marker for many Pseudomonas spp., by gas chromatography indicated that the bacterial biomass exceeded the viable counts by approximately 15 times. Fungi were grown on several occasions, the dominating genera being Fusarium and Candida. Soon after the old MWF was removed and the tank was provided with fresh MWF, which consisted of an emulsion of mineral oil in water, there was a massive growth of P. pseudoalcaligenes that reached levels of greater than 10(8) bacteria per ml. Initially, only low concentrations of other species were found for some weeks. After this period, different enterobacteria and other gram-negative rods often appeared at high concentrations (10(7) and 10(8) bacteria per ml, respectively). Bacteria identified as P. pseudoalcaligenes showed great variation with respect to colony morphology and a certain heterogeneity with respect to biochemical characteristics. Certain bacterial species grew as microcolonies on metal strips immersed in the circulating MWF, but P. pseudoalcaligenes was not recovered from this habitat. The total bacterial count in the air surrounding the machines in the metal-working shop showed an inverse relation to increasing distance from the machine. The concentration of bacteria in the air varied because of the number of machines in use, temperature, and humidity.(ABSTRACT TRUNCATED AT 250 WORDS)
Air Microbiology↗
Difference between bacterial and food antigens in mucosal immunogenicity.
The mucosa-associated lymphoid tissue may deviate from its systemic counterpart in being able to discriminate between microbial and nonmicrobial antigens. To study this, the systemic and mucosal antibody responses to bacterial and food antigens were followed in parallel in female rats during two pregnancies and lactation periods. Germfree rats were monocolonized with an Escherichia coli O6K13H1 strain, and their diet was switched to pellets containing large amounts of ovalbumin and beta-lactoglobulin. Antibodies against O6 lipopolysaccharide already appeared in serum and bile 1 week after colonization, and those against type 1 fimbriae appeared a few weeks later. Serum immunoglobulin G antibodies against the E. coli enzyme beta-galactosidase were found in moderate titers in all rats after 16 weeks of exposure. In contrast, few rats had detectable antibody levels against the dietary proteins ovalbumin and beta-lactoglobulin in serum or bile even after 16 weeks of exposure. In the milk, antibodies against E. coli beta-galactosidase and type 1 fimbriae reached the highest titers, while moderate titers were found against the food antigens and against O6 lipopolysaccharide. The difference in immune reactivity against bacterial versus dietary antigens was not likely due to insufficient amounts of the latter reaching lymphoid tissue, since (i) uptake studies indicated that ovalbumin was more efficiently taken up than endotoxin and (ii) the same difference in antigenicity between ovalbumin and E. coli was seen after immunization directly into Peyer's patches. We therefore suggest that a prerequisite for a strong mucosal antibody response is that the antigen be encountered by the gut-associated lymphoid tissue within microorganisms capable of stimulating antigen presentation.
Animals↗
Serum antibodies to Pseudomonas pseudoalcaligenes in metal workers exposed to infected metal-working fluids.
Metal workers exposed to aerosol from metal-working fluid were examined with respect to serum antibody to the lipopolysaccharide (LPS) of Pseudomonas pseudoalcaligenes. During 1 year of observation this species grew at high concentrations in the fluid (approximately 10(8) CFU/ml), and the air surrounding the metal-working machines sometimes contained more than 10(5) CFU/m3. The levels of antibody belonging to the IgG and IgA classes were significantly higher than in blood donors and in workers newly employed. Comparison with employees not working in the machine hall showed a significantly higher IgG, but not IgA, antibody level. For IgM antibody no such difference was found. Among the exposed workers, non-smokers had significantly higher IgG antibody levels than smokers, whereas no such difference was established for IgA and IgM antibodies. In smokers the IgG antibody level seemed to decline in the long-range time, since there was a negative correlation between the time of employment with exposure to metal-working fluids and IgG antibody level. The antibody data indirectly demonstrate that P. pseudoalcaligenes grown in metal-working fluid penetrated the body surface of metal workers to yield an immune response most probably after inhalation of aerosol containing bacteria. In the metal workers this long-term exposure did not lead to any acute or chronic respiratory discomfort.
Adult↗
Adherence, lipopolysaccharide and mucosal inflammation.
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Animals↗
Heterogeneity of lipid A: structural determination by 13C and 31P NMR of lipid A fractions from lipopolysaccharide of Escherichia coli 0111.
Purified lipid A from Escherichia coli 0111 was fractionated by thin-layer chromatography, and seven major bands were studied by 13C and 31P NMR. All lipid A fractions except one had fatty acids, 3-hydroxytetradecanoic acid, 3-(acyloxy)tetradecanoic acid, and phosphate groups bonded to the diglucosamine backbone. The remaining fraction was shown to be phosphatidylethanolamine. The number of substituents found showed that in all fractions all sites available for C-acylation (C-3, C-4, and C-3') and N-acylation (C-2 and C-2') carried acylic substituents. The number, ranging from four to six, and type of ester-bound carboxylic acid residues as well as the number of phosphate groups differed among the fractions. The three fastest moving bands all had three unsubstituted hydroxy fatty acids and one phosphate group (C-4'), while the slower moving bands had four hydroxy fatty acids and two phosphate groups. Unsubstituted 3-hydroxytetradecanoic acid residues were amide-bound to the disaccharide in all but one of the fractions. In summary, the heterogeneity of E. coli 0111 lipid A is found to be a consequence of a variation of the number and composition of carboxylic acid residues and of varying phosphate content.
Carbon↗
Lipid A fractions analyzed by a technique involving thin-layer chromatography and enzyme-linked immunosorbent assay.
A modified enzyme-linked immunosorbent assay (ELISA), with alkaline phosphatase as enzyme, was used for the study of antigenicity of lipid A fractions directly on thin-layer chromatographic (TLC) plates. For visualization a gel slab containing the enzyme substrate was placed on the plate containing enzyme-conjugated antibodies. The plate was read by a thin-layer chromatogram spectrophotometer. The immunoassay was both highly specific and quite sensitive. Sensitivity was superior to levels obtained by staining the plate with molybdenum blue (for phosphate) or orcinol (for carbohydrate). Fractions of lipid A from Escherichia coli 0111, Shigella flexneri or Salmonella minnesota R595, after being separated by thin-layer chromatography, were analyzed using rabbit anti-(lipid A) serum. Patterns obtained by scanning the same plates for phosphate staining and for the TLC-ELISA corresponded well. For comparison with TLC-ELISA, an inhibition assay was run using a tube ELISA. The tube ELISA, run in aqueous medium, showed that fractions 6-8 (those having the highest RF values) had the least activities. In contrast, TLC-ELISA did not detect large differences between fractions 2-7. This discrepancy probably reflected limited aqueous solubility of fractions 6 and 7. We conclude that TLC-ELISA might reveal antigenic activities of lipids that could be missed by other methods. The data suggested that all fractions, except for fraction 8, were similar in their antigenicity by TLC-ELISA. Differences in antigenicity between the fractions occurred when the fractions were tested in free form in an aqueous environment and these differences possibly could have been due to different solubilities of individual fractions.
Chromatography, Thin Layer↗
Heterogeneity of lipid A: comparison of lipid A types from different gram-negative bacteria.
Chloroform-soluble purified lipid A preparations from 10 sources, including five Escherichia coli strains (EH100, K-12, O127, O111, RCDC), two Salmonella strains (Salmonella typhimurium, Salmonella minnesota R595), Shigella sonnei II, and a hybrid of Shigella flexneri and E. coli K-12, were compared with lipid A from S. flexneri. Purified lipid A from S. flexneri was earlier found to be composed of eight fractions. The various lipid A preparations were assayed by thin-layer chromatography. Chromatograms were stained for phosphate or carbohydrate by molybdenum blue or orcinol, respectively. The number of major bands found for each lipid A preparation varied between 7 and 10, depending on the source. Comparable bands, based on Rf, were found among all of the different lipid A preparations, but the quantity of each band varied between the sources of lipid A. Four bands (designated 2, 3, 7, and 8) were abundant in every preparation. Variations of conditions used for preparing lipid A, such as changing of hydrolysis time, did not affect the appearance of lipid A on thin-layer chromatography. Change in the type of acid used for hydrolysis also did not affect the band pattern, but it did change the quantitative amounts of the various bands to some degree.
Chromatography, Thin Layer↗
Lipid A in anaerobic bacteria.
The ability of lipid A preparations from strains of Bacteroides, Fusobacterium, and Veillonella to inhibit the lipid A-anti-lipid A reaction in an enzyme-linked immunosorbent assay was tested. Anti-lipid A serum was prepared with lipid A from Salmonella minnesota R595, and lipid A from Escherichia coli EH100 was used as control antigen. Preparations from three of four different species of Bacteroides were unable to inhibit the anti-lipid A activity, whereas lipid A preparations from Fusobacterium and Veillonella strains inhibited 50% of the activity at 1 to 141 micrograms. One of the Bacteroides strains, Bacteroides oralis, showed a very weak inhibiting activity at the highest concentration used. The results confirm that Bacteroides species have a unique lipopolysaccharide structure, in contrast to other anaerobic genera which have a lipopolysaccharide structure similar to that of the Enterobacteriaceae.
Anaerobiosis↗
Studies of antibodies to lipid A and Tamm-Horsfall in patients with inflammatory bowel disease.
Sera from patients with inflammatory bowel disease, ulcerative colitis (UC), or Crohn's disease (MC) were analysed for antibodies to lipid A and Tamm-Horsfall protein (TH), Escherichia coli O antigens, and food antigens, using enzyme-linked immunosorbent assay, indirect haemagglutination, and thin-layer immunoassay, respectively. C-reactive protein (CRP), an indicator of acute inflammation, was also studied. The MC and UC groups were not separated by any of the factors tested. The extent of the disease, however, seemed to influence the IgG antibody response to lipid A and TH. Patients with extended inflammatory areas in the intestine had decreased anti-lipid-A levels during the active phase of the disease compared with patients with less inflammation. In contrast, the IgG anti-TH levels were increased in these patients during both the active and inactive phases compared with less affected patients. Compared with healthy individuals, MC or UC patients showed decreased IgG anti-lipid-A levels. Both IgG and IgA anti-TH and total anti-O levels were increased compared with controls. Antibodies to cow's milk were lower in patients with inflammatory bowel disease than in the control group. CRP was increased in patients with active inflammatory bowel disease compared with inactive.
Adolescent↗