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Biomedical subjects

K C Klasing

Publications and source records attributed to K C Klasing.

At least 37 records · Page 2Linked to original sources

Nutritional modulation of resistance to infectious diseases.

Dietary characteristics can modulate a bird's susceptibility to infectious challenges and subtle influences due to the level of nutrients or the types of ingredients may at times be of critical importance. This review considers seven mechanisms for nutritional modulation of resistance to infectious disease in poultry. 1) Nutrition may impact the development of the immune system, both in ovo and in the first weeks posthatch. Micronutrient deficiencies that affect developmental events, such as the seeding of lymphoid organs and clonal expansion of lymphocyte clones, can negatively impact the immune system later in life. 2) A substrate role of nutrients is necessary for the immune response so that responding cells can divide and synthesize effector molecules. The quantitative need for nutrients for supporting a normal immune system, as well as the proliferation of leukocytes and the production of antibodies during an infectious challenge, is very small relative to uses for growth or egg production. It is likely that the systemic acute phase response that accompanies most infectious challenges is a more significant consumer of nutrients than the immune system itself. 3) The low concentration of some nutrients (e.g., iron) in body fluids makes them the limiting substrates for the proliferation of invading pathogens and the supply of these nutrients is further limited during the immune response. 4) Some nutrients (e.g., fatty acids and vitamins A, D, and E) have direct regulatory actions on leukocytes by binding to intracellular receptors or by modifying the release of second messengers. 5) The diet may also have indirect regulatory effects that are mediated by the classical endocrine system. 6) Physical and chemical aspects of the diet can modify the populations of microorganisms in the gastrointestinal tract, the capacity of pathogens to attach to enterocytes, and the integrity of the intestinal epithelium.

Animal Feed↗

Effect of dietary energy level and oil source on broiler performance and response to an inflammatory challenge.

Broiler chicks were fed one of five diets from 3 d of age: a low energy diet containing 7% cellulose (ME 2,714 kcal/kg), or high energy diets containing approximately 7% of either tallow, corn oil, safflower oil, or fish oil (each 3,302 kcal/kg). Half of the chicks were injected intra-abdominally with Salmonella typhimurium lipopolysaccharide (LPS) on Day 11, sephadex on Day 13, and Freund's complete adjuvant on Day 15; samples were collected on Day 16. The uninjected chicks served as controls. In a second experiment, 3-d-old chicks were fed one of eight isocaloric diets containing tallow as the sole supplemental fat source, or tallow plus either 2% corn oil, 1, 1.5, or 2% fish oil, or fish meal at an amount to provide 1, 1.5 or 2% supplemental oil. Half of the chicks were injected intra-abdominally with S. typhimurium LPS on Days 10, 12 and 14; the uninjected chicks served as controls. Samples were taken on Day 15. In Experiment 1, the cellulose diet decreased performance to 10 d of age relative to the other diets, whereas immunogen injection decreased weight gain and feed efficiency and increased indices of inflammation among all dietary groups. Fish oil at approximately 7% of the diet did not improve weight gain. Fish oil diets improved weight gain and feed efficiency in Experiment 2 relative to the other diets, in spite of minimal effects on indices of inflammation. Injection of LPS decreased performance and increased inflammation across dietary treatment, although the second LPS injection was less potent in altering performance responses and inflammation compared to the first injection, indicating that repeated injections of LPS amy cause the chicks to become refractory to that stimulus. The fish meal diets resulted in poorer performance than similar levels of lipid provided as fish oil. Lower levels of dietary fish oil were more efficacious in improving broiler performance than higher levels, and fish oil provided from fish meal was not as efficacious as oil per se, possibly due to nonlipid components of the meal.

Animals↗

Regulation of cytokine-induced neutrophil chemoattractant in rat bone marrow-derived macrophages by inflammatory mediators.

During the course of inflammation, macrophages are highly influenced by their local environment and changes in the cytokine milieu. Exposure of macrophages to various factors during different phases of the inflammatory response may have a strong influence on the pattern of gene expression, which a macrophage exhibits. We examined how these mediators affect the regulation of the expression and production of cytokine-induced neutrophil chemoattractant (CINC). Our study demonstrates that CINC can be induced in bone marrow-derived macrophages by lipopolysaccharide, interleukin-1 beta, tumor necrosis factor-alpha (TNFalpha), and interferon-gamma/TNF alpha. These mediators are factors which a macrophage would be expected to encounter early in an inflammatory process. In contrast, transforming growth factor-beta (TGFbeta), which is expressed late in the inflammatory process during mesenchymal cell proliferation and tissue repair, did not induce detectable amounts of CINC and functioned to suppress CINC production stimulated by early inflammatory mediators. Suppression of CINC production occurred whether TGF beta was added simultaneously, 12 or 24 h prior to the stimulus.

Animals↗

Dietary fish oil alters specific and inflammatory immune responses in chicks.

Two experiments were designed to determine the effects of dietary (n-3) fatty acids and grain source on the growth-suppressive effects of the inflammatory response and indices of specific immunity. In Experiment 1, chicks were fed diets containing 0.5, 1, or 2 g/100 g of either corn oil or fish oil. In Experiment 2, chicks were fed diets containing up to 2 g/100 g of either fish oil, linseed oil or corn oil as the source of dietary fat, in either cereal grain- or corn-based diets. In each experiment, subsets of chicks within each dietary treatment were either vaccinated with infectious bronchitis virus (IBV) vaccine, injected with Salmonella typhimurium lipopolysaccharide (LPS), heat-killed Staphylococcus aureus, or remained noninjected. Increasing dietary fish oil, but not corn oil increased body weight and lessened the growth-suppressing effect of heat-killed S. aureus or S. typhimurium LPS. Increasing the concentration of dietary fish oil decreased febrile response, circulating hemopexin and metallothionein concentrations. Dietary fish oil resulted in decreased release relative to dietary corn oil of interleukin-1 by peritoneal macrophages. Although IBV titers were not significantly affected by dietary oil treatment, phytohemagglutination-induced wattle swelling was greater among chicks fed fish oil. In Experiment 2, the modulating effects of fish oil on the immune system were dependent on the type of grain used in the diet, with fish oil/cereal diets resulting in greater cell-mediated immunity and lower indices of inflammation than fish oil/corn diets. Inclusion of increasing amounts of fish oil in the diet improved performance, decreased indices of the inflammatory response and either improved or did not change indices of the specific immune response of growing chicks.

Animals↗

Dietary fish oil or lofrin, a 5-lipoxygenase inhibitor, decrease the growth-suppressing effects of coccidiosis in broiler chicks.

Broiler chicks were fed a diet containing 4% of either corn oil or fish oil from 3 to 14 d of age. From Days 15 to 23, half of the chicks in each dietary treatment were fed Lofrin (an experimental 5-lipoxygenase inhibitor) at 33 micrograms/kg feed. The remaining chicks within each dietary treatment were the untreated controls. At 24 d of age, half of the chicks within each diet-Lofrin treatment group were each infected with 4.6 x 10(4) sporulated Eimeria tenella oocysts, resulting in a 2 x 2 x 2 factorial arrangement of treatments. Body weight gain, feed consumption, and feed conversion efficiency were determined throughout the study. At 27 d of age, blood, liver, and ceca were sampled. Plasma tumor necrosis factor and hemopexin, hepatic fatty acid composition, and cecal inflammatory cell infiltration were determined. Liver fatty acid composition tended to reflect that of the diet. Chicks fed fish oil had livers that were enriched in (n-3) polyunsaturated fatty acids (PUFA) at the expense of (n-6) PUFA. Chicks fed fish oil gained body weight more rapidly than those fed corn oil. Infection of chicks with Eimeria decreased body weight gain of chicks fed corn oil, but not of chicks fed fish oil. The addition of Lofrin to the corn oil diets abrogated the growth-suppressing effects of infection, although there was no Lofrin effect among chicks fed fish oil. There was a diet by Lofrin interaction in which Lofrin treatment of birds fed corn oil decreased feed consumption and increased feed conversion efficiency, but had no effect on chicks fed diets containing fish oil. Plasma hemopexin was greater, but tumor necrosis factor was lower, in chicks fed fish oil than in chicks fed corn oil. Eimeria infection significantly increased cecal inflammatory cell infiltration across all dietary treatments. There were no clear relationships between growth rate or efficiency and the severity of the inflammatory response to Eimeria infection, as indicated by hemopexin levels and cecal inflammatory scores. These results indicate that Lofrin or fish oil, both of which modify eicosanoid metabolism, attenuate the growth-depressing effects of an Eimeria tenella infection.

Aging↗

Dietary copper level affects copper metabolism during lipopolysaccharide-induced immunological stress in chicks.

Two experiments were conducted to examine the effect of dietary Cu level on Cu metabolism during the acute phase response in broiler chicks with adequate (Experiment 1) or deficient (Experiment 2) Cu. Diets based on cornstarch and isolated soybean protein were used to formulate a basal diet, and basal diet plus either 5, 10, or 15 mg/kg additional Cu as either CuO or CuSO4. Each diet was fed to six pens of five chicks per pen (Experiment 1) or eight pens of five chicks (Experiment 2). Half of the chicks on each diet were injected with Salmonella typhymurium lipopolysaccharide (LPS) on alternate days. In Experiment 1, LPS significantly decreased daily gain, feed intake, and feed efficiency (P < 0.01) and increased the concentration of Cu in blood plasma (P < 0.01). In the uninjected birds, adding 5, 10, or 15 mg/kg Cu as CuO or 15 mg/kg Cu as CuSO4 increased the rate of gain over that of chicks fed the basal diet. In the birds challenged with LPS, 10 mg/kg Cu as CuO increased the rate of gain and efficiency compared to those of chicks fed the basal diet. Addition of CuSO4 to the diet of chicks challenged with LPS did not affect gain, intake, or feed efficiency compared to those of chicks fed the basal diet. Ceruloplasmin levels were higher in chicks challenged with LPS than in control chicks (P = 0.03), and this difference tended to be greater in chickens fed CuO than in chickens fed CuSO4 (P = 0.07). In chicks challenged with LPS, feeding CuO at all levels and feeding CuSO4 to give 10 or 15 mg/kg Cu increased ceruloplasmin levels above that of chicks fed the basal diet. Hepatic Mn superoxide dismutase (SOD) and Cu/Zn SOD were not influenced by dietary Cu level or source or LPS. Results of Experiment 2 were similar to those of Experiment 1 except that supplemental CuSO4 and CuO gave similar increases in gain and CuSO4 was more effective at increasing ceruloplasmin levels. Chicks given supplemental Cu had higher ceruloplasmin levels following challenge with LPS than Cu-deficient chicks fed the basal diet. Apparently, Cu requirements are higher for chicks experiencing an acute phase response than for healthy chicks.

Acute-Phase Reaction↗

Cytokine-induced neutrophil chemoattractant production by primary rat alveolar type II cells.

This study was designed to determine the production of the chemokine cytokine-induced neutrophil chemoattractant (CINC) by primary rat alveolar type II (ATII) cells upon stimulation with exogenous and endogenous proinflammatory factors. Cultures of primary rat ATII cells were exposed to lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF alpha) over a 16 hour period and the production of CINC both apically and basolaterally was measured by ELISA. Compared to unstimulated (UNS) cultures, LPS, IL-1 beta and TNF alpha were found to significantly increase the level of CINC detected in culture by two, four and sixteen hours post stimulation, respectively. ATII cells also demonstrated a polar secretion of CINC. The accumulation of CINC basolaterally was significantly more than apically; 133%, 45%, 117% and 123% for UNS, IL-1 beta, LPS and TNF alpha respectively. We demonstrated that primary rat ATII cells may participate in the chemokine network during inflammation by the production of CINC upon stimulation with endogenous and exogenous factors.

Animals↗

Methionine deficiency decreases protein accretion and synthesis but not tRNA acylation in muscles of chicks.

The effect of supplementing a methionine-deficient, isolated soy protein diet (0.5% total sulfur amino acids) with 0.2% D,L-methionine (DL-MET) or a molar equivalent of D,L-2-hydroxy-4-(methylthio) butanoic acid (DL-HMB) was assessed in chicks over an 8-d feeding study. Chicks consumed DL-HMB diet ad libitum (HIGH) or were restricted to the level consumed ad libitum by chicks fed the basal diet. The DL-MET diet was fed at the same two levels as the DL-HMB diet. Supplementing with either methionine source resulted in significantly greater growth rate, efficiency of feed conversion, and accretion and synthesis of protein in the gastrocnemius and pectoralis muscles. These increases were greater for chicks consuming feed ad libitum as compared with feed-restricted chicks and were not affected by methionine source. Rate of muscle protein degradation appeared to increase with supplementation of either methionine source, but only when feed intake was permitted to increase. The relative in vivo conversion of DL-HMB vs. D-MET to L-MET was similar in all groups as indicated by pool sizes of methionine, tRNA(met), and tRNA(cys), and rates of protein accretion and synthesis. These data demonstrate that dietary DL-HMB and DL-MET are used with similar efficacy to support skeletal muscle protein accretion and rates of protein synthesis when feed intake is equalized.

Acylation↗

Diet-dependent and diet-independent metabolic responses underlie growth stasis of pigs at weaning.

The weaning transition in domestic animals involves profound environmental and nutritional changes. Growth stasis is commonly observed in pigs during this period, resulting in significant losses to the swine industry. It has been suggested that the reduced growth rate reflects immune sensitivity to soy antigens in commercial diets; however, few studies have defined metabolic responses in pigs weaned to diets containing soybean meal. The impact of environmental and social changes at weaning on physiological functions, i.e., the metabolic adjustment to new nutritional substrates, has also been overlooked. Accordingly, the aim of this study was to distinguish diet-dependent and diet-independent metabolic responses in pigs weaned to a commercially available corn-soy diet. Focus was on the endocrine pancreas and cytokines associated with stress responses. Three-week-old crossbred pigs were weaned to a corn-soy (cereal) or a milk-based (milk) diet. Blood samples taken 0 (weaning), 1, 2, 5 and 7 d post-weaning demonstrated diet-independent responses including increased (P < 0.05) plasma glucagon concentrations, decreased (P < 0.05) glucose concentrations, increased (P < 0.05) interleukin-1 (IL-1) concentrations during the first 2 d post-weaning, and increased (P < 0.05) fibrinogen concentrations during the latter part of the study. In response to dietary treatment, milk-fed pigs had higher (P < 0.05) plasma insulin and glucose concentrations, reflective of higher food intake during the early post-weaning period. This clear distinction between diet-dependent and diet-independent metabolic responses at weaning suggests consideration of novel strategies to overcome the characteristic weanling growth stasis in pigs.

Animals↗

Serotransferrin, ovotransferrin and metallothionein levels during an immune response in chickens.

Extracellular iron-binding proteins function in iron transport, iron scavenging and bactericidal activity. To determine whether the levels of chicken iron-binding proteins are altered during an immune challenge, young broiler chicks and 40-week-old hens were injected with lipopolysaccharide (LPS). Serum transferrin and liver mRNA for serum transferrin increased at 24 hr after injection. Increased levels of serum transferrin and hepatic mRNA for serum transferrin define chicken serum transferrin as an acute-phase protein. Magnum mRNA for ovotransferrin decreased 24 hr after the immune challenge in hens. Hens had also stopped ovulating, suggesting that synthesis of all egg proteins was decreased.

Animals↗

Avian leukocytic cytokines.

Leukocytic cytokines are produced by cells of the immune system and are prominent regulators of the immune response and in some cases various systemic responses. Leukocytic cytokines are released during immune responses and may act in autocrine, paracrine, or endocrine manners. Although over a dozen avian leukocytic cytokines have been described based on functional activities, characterization at the molecular level is not well developed. Two exceptions are 1) myelomonocytic growth factor, a colony-stimulating factor-like cytokine required for the growth and differentiation of hematopoietic precursor cells, particularly myelomonocytic cells; and 2) the avian transforming growth factor-beta (TGF-beta) family of cytokines, which modulate wound healing, bone metabolism, and cellular differentiation. Cytokines with bioactivities similar to mammalian interleukin (IL)-1, IL-2, IL-6, and interferon-gamma have been at least partially purified. Cytokines with bioactivities similar to mammalian IL-8, colony-stimulating factor, and tumor necrosis factor-alpha have been reported but are not well characterized at the molecular level. With a few exceptions, including TGF-beta and thymulin, highly purified leukocytic cytokines of mammalian origin have diminished or no specific activity in avian assay systems. The chicken IL-1 receptor has been cloned and the predicted amino acid sequence shares 60% homology with the human IL-1 receptor. A component of the chicken IL-2 receptor has been partially purified but little is known about other avian leukocytic cytokine receptors. Potential applications of leukocytic cytokines in poultry production originate from their regulation of a variety of functions such as disease resistance, would healing, bone accretion, nutrient partitioning, appetite, growth, and reproduction.

Animal Husbandry↗

Dietary energy source and density modulate the expression of immunologic stress in chicks.

To determine how dietary energy level and source influence feed intake, growth and energy partitioning drug immunologic stress, growing chicks were fed diets based on cornstarch and casein with varying energy densities and injected every other day for 6 d with either saline (control), Salmonella typhimurium lipopolysaccharide or heat-killed Staphylococcus aureus. Salmonella typhimurium lipopolysaccharide decreased growth and feed consumption at low energy densities. When the dietary energy density was increased above 13.4 kJ/g using cornstarch, but not corn oil, the growth depressing effect of immunogens was eliminated. Immunologically stressed chicks had a greater proportion of gain in visceral organs and less in the carcass, regardless of the nutrient density of the diet. Immunologic stress decreased intake of metabolizable energy of chicks fed a diet with low nutrient density and increased it for those fed a diet with high nutrient density. Chicks injected with S. typhimurium lipopolysaccharide lost more energy as heat than controls when differences in metabolizable energy intakes were accounted for and modified their preference between two diets differing in metabolizable energy density and fat content as a result of the challenge. Control chicks selected between the 11.7 and 14.2 kJ/g diets to obtain an energy density of 13.2 kJ/g compared with 12.5 kJ/g in the S. typhimurium lipopolysaccharide-challenged chicks. The S. typhimurium lipopolysaccharide-challenged chicks consumed similar amounts of the low energy diet but decreased intake of the high energy diet.

Animals↗

Source of amino acids for tRNA acylation. Implications for measurement of protein synthesis.

Estimates of protein-synthesis rates using radioisotopes require accurate measurement of the specific radioactivity of the label in protein and in the precursor pool over time. Although the extracellular and intracellular pools of amino acids are easiest to sample, the tRNA pool is the direct precursor and is the appropriate pool for sampling. To test if the intracellular or extracellular pools reflect the tRNA specific radioactivity, a chicken macrophage cell line was incubated in medium containing either 0.23 mM-leucine and 14.5 microCi of [3H]leucine (tracer dose) or 2.3 microM-leucine plus 145.0 microCi of [3H]leucine (flooding dose). At both leucine levels, the tRNA specific radioactivity reached a plateau quickly, but did not equilibrate with either the extracellular or intracellular specific radioactivity within 30 min, and remained closer to that of protein. In a second experiment, proteins in chicken macrophages were labelled with [3H]leucine for 2 days. Labelling medium was removed, and the cells were washed free of residual free [3H]leucine and incubated with medium containing either 0.23 mM- or 2.3 mM-leucine (unlabelled). The specific radioactivity of leucyl-tRNA leucine reached a plateau within 2 min and remained considerably closer to that in the protein than that in intracellular or extracellular pools for at least 60 min. These results suggest that amino acids from protein degradation are a primary source for charging tRNA. When protein-synthesis rates are estimated by label incorporation, use of extracellular or intracellular specific-radioactivity values result in a marked underestimation.

Acylation↗

Prevention of immunologic stress contributes to the growth-permitting ability of dietary antibiotics in chicks.

The growth-permitting ability of antibiotics fed to broiler chicks was studied as it relates to the state of activation of the immune system. In Experiment 1, chicks were fed two levels of antibiotics (0 or 100 mg streptomycin + 100 mg penicillin/kg diet) and were raised either in an environment with poor sanitation to create a chronic immune stress or in a clean environment. Chicks raised in the unsanitary environment and not fed antibiotics had significantly lower (P < 0.05) rates of weight gain and efficiencies of feed utilization, and higher levels of plasma interleukin-1, compared with chicks raised in the clean environment or chicks raised in the unsanitary environment and fed antibiotics. Adding antibiotics to the diet of birds in the clean environment did not affect any variable. In Experiment 2, chicks were raised in a conventional environment and fed two levels of an antibiotic (0 or 100 mg tetracycline/kg diet). After a 15-d feeding period, half of the chicks were injected with Salmonella typhimurium lipopolysaccharide to create an acute immunologic stress. Feeding antibiotic resulted in improved weight gain, feed consumption and efficiency of feed utilization. Lipopolysaccharide-injected birds developed heavier livers, spleens and intestines relative to body weights and higher rectal temperatures and hepatic metallothionein concentrations, presumably due to an immunologic stress. Omitting antibiotic from the diet resulted in similar changes. These results indicate that feeding antibiotics may permit growth by preventing immunologic stress and associated metabolic changes brought about by monokines including interleukin-1.

Animals↗

Avian inflammatory response: mediation by macrophages.

The inflammatory response is one of the best defined components of nonspecific immunity in birds. Introduction of an immunogen into the skin or peritoneal cavity results in a characteristic series of local and systemic responses. Initially, locally produced chemotactic substances cause heterophils and monocytes to emigrate from the blood through postcapillary venules to the site of immunogen. Monocytes and heterophils phagocytize the immunogen and monocytes can initiate specific immunity mediated by lymphocytes. Monocytes release a variety of hormone-like substances (monokines) that act locally to coordinate the localized inflammatory response and facilitate lymphocyte responses. These same monokines can gain entrance into the circulation and act systemically to orchestrate the acute phase response. Monokine activities characterized to date are similar to mammalian interleukin-1, interleukin-2, tumor necrosis factor, and granulocyte-stimulating factor. The inflammatory response is active in the embryo midway through incubation and is probably instrumental in protection of the embryo. Inappropriate or overexuberant inflammatory responses can lead to a variety of pathologies in the chicken, demonstrating the importance of precise regulation of the inflammatory response.

Animals↗

Monokines in growth and development.

Stimulation of the immune system results in a series of metabolic changes that are antagonistic toward growth. Monokines, including interleukin-1, tumor necrosis factor, and interleukin-6, are released from cells of the monocyte-macrophage lineage after recognition of immunogens. They appear to mediate homeorhetic response, which alters the partitioning of dietary nutrients away from growth and skeletal muscle accretion in favor of metabolic processes which support the immune response and disease resistance. These alterations include 1) decreased skeletal muscle accretion due to increased rates of protein degradation and decreased protein synthesis; 2) increased basal metabolic rate resulting in increased energy utilization; 3) use of dietary amino acids for gluconeogenesis and as an energy source instead of for muscle protein accretion; 4) synthesis by the liver of acute phase proteins; 5) redistribution of iron, zinc, and copper within the body due to the hepatic synthesis of metallothionein, ferritin, and ceruloplasmin; (6) impaired accretion of cartilage and bone; and 7) release of hormones such as insulin, glucagon, and corticosterone. These monokines also influence the differentiation of cells. Tumor necrosis factor suppresses the differentiation of myoblasts and adipocytes whereas the chicken monokine myelomonocytic growth factor induces the differentiation of granulocytes.

Acute-Phase Proteins↗

Roles of synthesis and degradation in the regulation of metallothionein accretion in a chicken macrophage-cell line.

Metallothionein (MT) is a metal-binding protein rapidly accreted in many tissues in response to trace elements or hormones. To gain an understanding of the regulation of MT accretion, rates of MT synthesis and degradation were determined by using a decay-kinetics technique. A chicken macrophage-cell line (HD11) that rapidly accretes incremental amounts of MT when stimulated with increasing concentrations of Zn2+ or Cd2+ was studied. The maximum rate of MT accretion occurred at 50 microM-Zn2+ or 20 microM-Cd2+. The absolute rate of MT accretion was less in macrophages incubated with 25 microM- as compared with 50 microM-Zn2+, owing to decreased and increased rates of MT synthesis and degradation respectively. The absolute rate of MT accretion was less in macrophages incubated with 10 microM- as compared with 20 microM-Cd2+, owing to a decreased rate of MT synthesis with no change in degradation. Compared with macrophages continually incubated with 50 microM-Zn2+, removal of Zn2+ from medium previously containing 50 microM-Zn2+ decreased the absolute rate of MT accretion, owing to decreased and increased rates of MT synthesis and degradation respectively. Removal of Cd2+ from medium previously containing 20 microM-Cd2+ also decreased the absolute rate of MT accretion in macrophages. Unlike Zn2+ removal, the decrease in MT accretion was due to a decreased rate of MT synthesis with no change in degradation. When macrophages incubated with 50 microM-Zn2+ were subsequently incubated with 20 microM-Cd2+, rates of MT synthesis and accretion were decreased as compared with cells continually incubated with 50 microM-Zn2+ or 20 microM-Cd2+. When macrophages incubated with 20 microM-Cd2+ were subsequently incubated with 50 microM-Zn2+, rates of MT synthesis and accretion were increased as compared with cells continually incubated with 50 microM-Zn2+ or 20 microM-Cd2+. Switching the metal in the incubation medium did not influence the rate of MT degradation. Our results indicate that the rate of MT accretion is determined by variations in the rates of MT synthesis and degradation, depending upon the inducing metal and the concentration of the metal.

Animals↗