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PubMed1989

Endotoxin levels in farming: absence of symptoms despite high exposure levels.

The endotoxin concentration in air was measured in farms where 11 farmers had experienced febrile reactions or allergic alveolitis and in a random sample of farms with 17 symptomless farmers. Samples were obtained during normal dairy farming in eight reference farms (background samples) and in all farms during the handling of material which had probably caused symptoms or disease or, in reference farms, maximal spore exposure (worst case samples). In addition, parallel samplers were used in reference farms, one with a cyclone (5 microns cutoff) and one without, to measure the dust and endotoxin concentrations in the respirable fraction and total dust. The endotoxin worst case values varied from less than 0.01 to greater than 50 micrograms/m3 in symptom farms (median 6.4 micrograms/m3, geometric mean 2.2 micrograms/m3) and from less than 0.01 to greater than 50 micrograms/m3 in reference farms (median 42 micrograms/m3, geometric mean 29 micrograms/m3). This difference was not statistically significant. The background values in reference farms were 1.3 (median) and 0.4 (geometric mean) micrograms/m3. The differences between samples with and without cyclone and between background and worst case samples were statistically significant (p less than 0.02). About 75% of the activity was found in the non-respirable fraction. No correlation was found between exposure to endotoxin and symptoms in farmers. There were weak, but statistically significant, correlations between endotoxin concentrations and total spore count or dust concentrations. The surprisingly high endotoxin values in the respirable fraction of air from environments which apparently did not cause symptoms raises the concern that the Limulus amebocyte assay might be sensitive to other components in the dust rather than endotoxin.

Agricultural Workers' Diseases↗

PubMed1991

Airway oedema and obstruction in guinea pigs exposed to inhaled endotoxin.

Protein extravasation and airway conductance (SGaw) were examined in awake guinea pigs exposed to inhaled endotoxin or saline for three hours. A significant increase in protein extravasation (as estimated by the leakage of protein bound Evans blue dye) was seen in the conducting airways of endotoxin exposed animals compared with saline exposed animals. Mean dye extravasation was significantly increased by one to threefold in the mainstem and hilar bronchi of endotoxin exposed animals. These changes in extravasation were accompanied by decrements in pulmonary function and by an influx of polymorphonuclear leucocytes into the airway wall. The SGaw decreased significantly by 60-90 minutes into exposure to endotoxin and had decreased by 22% and 34% at the end of exposure in the low and high dose endotoxin groups, respectively. Similar findings were obtained in animals exposed to cotton dust. Contrary to studies suggesting that platelet activating factor (PAF) is involved in the systemic and peripheral lung effects of endotoxin, pretreatment with the PAF antagonist WEB2086 did not prevent the conducting airway injury produced by inhaled endotoxin.

Aerosols↗

PubMed1992

Rapid diagnosis of gram negative pneumonia by assay of endotoxin in bronchoalveolar lavage fluid.

BACKGROUND: Diagnosis of ventilator associated pneumonia can be made by quantitative cultures of bronchoalveolar lavage fluid or of protected specimen brushings, though cultures require 24-48 hours to provide results. In 80% of cases aerobic Gram negative bacteria are the cause. METHODS: A rapid diagnostic method of assessing the endotoxin content of lavage fluid by Limulus assay is described. Forty samples of lavage fluid were obtained from patients with multiple trauma requiring mechanical ventilation for a prolonged period. Pneumonia was diagnosed on the basis of clinical, radiological, and bacteriological findings, including quantitative cultures of lavage fluid. RESULTS: A relation was observed between the concentration of endotoxin in lavage fluid and the quantity of Gram negative bacteria. The median endotoxin content of lavage fluid in Gram negative bacterial pneumonia was 15 endotoxin units (EU)/ml; the range observed in individual patients was 6 to > 150 EU/ml. In patients with pneumonia due to Gram positive cocci and in non-infected patients the median endotoxin level was 0.17 (range < or = 0.06 to 2) EU/ml. An endotoxin level greater than or equal to 6 EU/ml distinguished patients with Gram negative bacterial pneumonia from colonised patients and from those with pneumonia due to Gram positive cocci. CONCLUSION: The measurement of endotoxin in lavage fluid is a rapid (less than two hours) and accurate diagnostic method. It should allow specific and early treatment of Gram negative bacterial pneumonia.

Bronchoalveolar Lavage Fluid↗

PubMed1998

Expression of a Bacillus thuringiensis delta-endotoxin gene by Bacillus pumilus.

The delta-endotoxin genes from Bacillus thuringiensis were introduced into a rhizosphere-inhabiting Bacillus pumilus isolate to create a delta-endotoxin expression and delivery system for subterranean feeding insects such as the larvae of pale western cutworm (Agrotis orthogonia Morrison (Lepidoptera: Noctuidae)). Preliminary experiments indicated that Bacillus thuringiensis subsp. kurstaki cultures were toxic to pale western cutworm larvae. Three different cry genes from Bacillus thuringiensis subsp. kurstaki were cloned into high and low copy number vectors and mated into Bacillus pumilus RB8. When carried on high copy number vectors, cry genes appeared to inhibit sporulation and delta-endotoxin production in Bacillus pumilus RB8 cultures, since microscopic examination of these cultures revealed that < 0.1% of the cells of late stationary phase cultures had sporulated and produced parasporal inclusions. On low copy number vectors, the cry genes did not inhibit sporulation; however, production of delta-endotoxins was undetectable. Using a heat shock regime for enrichment of sporogenous crystalliferous variants, a Bacillus pumilus isolate, carrying cryIA(c) on a high copy number plasmid, was obtained in which high level delta-endotoxin production occurred concomitant with sporulation. Synthesis of functional delta-endotoxin by this strain was confirmed by Western blot analysis and bioassay with pale western cutworm larvae. These results show that rhizosphere-inhabiting bacilli are indeed a potential route for introduction of delta-endotoxins to the root environment for biocontrol purposes.

Animals↗

PubMed1983

Renal blood flow in normal dogs and in dogs with experimental liver cirrhosis following the acute continuous infusion of endotoxin.

The purpose of this study was to determine if the renal circulation of normal and cirrhotic dogs behave similarly in response to an acute endotoxin infusion. Endotoxin was administered as a slow continuous infusion (13-26 micrograms/min) to a total of 20 normal dogs through the femoral vein, portal vein, or into the left renal artery. In each case, there was an initial increment in renal blood flow, of the order of 46%, while arterial blood pressure was actually declining. After 8-20 min, blood flow fell as perfusion pressure declined further. The initial increment in renal perfusion was not due to a hyperthermic response following the endotoxin. When similar doses were given to five dogs with chronic biliary cirrhosis and ascites, the biphasic response in renal perfusion was not observed, rather blood flow declined as perfusion pressure declined. When normal dogs were infused with bilirubin, bile salts, noradrenaline, and angiotensin in pressor doses, the subsequent infusion of endotoxin still produced the usual biphasic response in renal perfusion. Chronic elevation of portal pressure (but not acute elevation), volume contraction by diuresis or hemorrhage, and the infusion of bile intravenously, all abolished the biphasic response in renal perfusion and reproduced in normal dogs the response to endotoxin observed in cirrhotic dogs. Investigation of the factors causing the initial decrease in intrarenal vascular resistance in normal dogs following the endotoxin infusion implicated a role for histamine, kinins, and prostaglandins. We conclude there is a fundamental difference in the response of the renal circulation of normal and cirrhotic dogs to an endotoxin infusion, which may depend on failure of this latter group to release one or more humoral agents. This difference may be due to elevated portal pressure, a decreased effective arterial blood volume, or the products of bile having access to the circulation in cirrhotic dogs.

Animals↗

PubMed1987

Endotoxin increases superoxide dismutase in cultured bovine pulmonary endothelial cells.

Manganous (Mn) and copper zinc (CuZn) superoxide dismutase (SOD) concentrations and glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured in cultured bovine pulmonary endothelial cells with and without exposure to Escherichia coli endotoxin (10(-1) micrograms/ml) over intervals of 0.5-24 h. The activities of two mitochondrial marker enzymes, fumarase and cytochrome-c oxidase, were also measured. Endotoxin exposure caused a marked increase (9-fold) in endothelial cell Mn SOD content without significant effects on GSH-Px, CAT, fumarase, or cytochrome-c oxidase activities. Endotoxin induced a slight decrease in CuZn SOD content over 24 h. This is the first report of a selective effect of endotoxin on Mn SOD in pulmonary endothelial cells. The response appears to be independent of an increase in mitochondrial activity (no change was observed in cytochrome-c oxidase or fumarase activities). These findings support the notion that endotoxin increases generation of toxic oxygen metabolites within pulmonary endothelial cells. An endotoxin-induced increase in Mn SOD could contribute to the reported protective effect of endotoxin against oxygen toxicity in these cells.

Animals↗

PubMed1996

Stable expression of a human HSP70 gene in a rat myogenic cell line confers protection against endotoxin.

Recent reports show that a pre-heat shock has a protective effect against endotoxin "in vivo" in rodents. It has remains unclear what actually confers the protection against endotoxin. One candidate for this protective effect is the heat shock protein of 70 kDa (HSP70). We found that a mild heat shock pretreatment is the rat myogenic cell line, H9c2(2-1), confers resistance to a subsequent exposure to endotoxin. A myogenic rat cell line stably transfected with the human inducible HSP70 exhibits an increased survival rate compared with cells stably transfected solely with the selectable neomycin marker gene or the parental cell line H9c2(2-1) when exposed to endotoxin. The mechanism of endotoxin-induced cell injury is postulated to be through the generation of nitric oxide in these myogenic cells during exposure to endotoxin. We conclude that HSP70, regardless of the particular mechanism of cytotoxicity, plays a role in protecting the cell against the deleterious effects of endotoxin.

Animals↗

PubMed1988

Pituitary-adrenal response to bacterial endotoxin in developing rats.

The neonatal rat is very sensitive to the lethal effects of bacterial endotoxin. Because of the adaptive importance of pituitary-adrenal secretions to stress, this study examined the ontogeny of the plasma corticosterone and adrenocorticotropic hormone (ACTH) responses to endotoxin. The lethal sensitivity of young rats to endotoxin ranged from 0.5 to 30 mg/kg (ip) in the 1- to 21-day-old rat. After endotoxin treatment, the 1- and 2-day-old rat showed marked elevations of corticosterone similar in magnitude to that seen in 21-day-old and adult rats; however, significantly depressed corticosterone increments were observed in the 5-, 10-, and 14-day-old rats. This age-related pattern of adrenocortical secretion was correlated with the developing rat's corticosterone response to exogenous ACTH. In contrast, endotoxin administered to 5-, 10-, and 14-day-old rats resulted in increments of plasma ACTH similar to those observed in the 21-day-old and adult rats. Although plasma ACTH levels increased by 84-127% in the 1- and 2-day-old rats, these increases were significantly less than those of rats at all other ages tested. Thus the newborn rat mounts an effective corticosterone response to endotoxin, loses this ability between ages 5-14 days, and regains this response at 21 days of age. Because the hyporesponsive ages exhibit a marked increase in ACTH secretion, the loss of the adrenocortical response to endotoxin appears to be a result of a depressed responsiveness of the adrenal cortex to ACTH.

Adrenocorticotropic Hormone↗

PubMed1993

Attenuation of endotoxin-induced intestinal microcirculatory damage by eicosapentanoic acid.

The major objective of this study is to investigate whether oral administration of eicosapentanoic acid (EPA) has any preventive effect on endotoxin-induced microcirculatory damage of rat small intestine. EPA in a daily dose of 300 mg/kg was orally given to male Wistar rats for 3 wk. Submucosal microvessels of the ileum were observed by intravital microscopy equipped with a high-speed video camera system after the intra-arterial infusion of endotoxin at a dose of 2 mg.kg-1.h-1. The number of sticking leukocytes was significantly increased at 30 min after the treatment of endotoxin especially along the smaller branch of intestinal venules. It reached the maximal plateau at 45 min after treatment. The pretreatment of EPA significantly attenuated the increase in sticking leukocytes induced by endotoxin. A platelet-activating factor (PAF) antagonist 2-[N-acetyl-N-(2-methoxy-3-octadecylcarbamoyloxy propoxycarbonyl) aminomethyl]-1-ethylpyridinium chloride (CV-6209) significantly prevented the increased leukocyte sticking to the same extent as EPA treatment. Thirty minutes after endotoxin infusion, red blood cell (RBC) velocity was significantly decreased in both arterioles and venules. RBC velocity appeared to be continuously decreased thereafter and reached its minimum value at approximately 60 min. EPA treatment was revealed to prevent the decrease in RBC velocity of microvessels induced by endotoxin. CV-6209 also significantly attenuated the decreased RBC velocity. The remarkable elevation of PAF content in the ileal mucosa as observed by endotoxin infusion was also significantly attenuated by administration of EPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1978

Procoagulant activity of peritoneal leukocytes: effects of cortisone and endotoxin.

Procoagulant activity of peritoneal leukocytes from rabbits given cortisone acetate, endotoxin, and both materials was measured in studies designed to test the hypothesis that cortisone acetate prepares rabbits for the generalized Shwartzman reaction by enhancing leukocyte procoagulant activity. Two types of peritoneal leukocyte suspensions were examined: mixed granulocyte-macrophage suspensions and macrophage suspensions. In both types, procoagulant activity could be accounted for by the number of macrophages in the suspensions. Cortisone alone did not affect the procoagulant activity, whereas endotoxin increased the procoagulant activity. Suspensions from animals given both cortisone and endotoxin varied in activity depending upon cell composition. Granulocyte-macrophage suspensions had less apparent procoagulant activity than suspensions with endotoxin alone. In contrast, macrophage suspensions--particularly sonicated suspensions--had greater procoagulant activity than those with endotoxin alone. The ability of cortisone acetate to increase macrophage procoagulant activity after endotoxin could represent one mechanism whereby cortisone acetate prepares rabbits for the generalized Shwartzman reaction after endotoxin.

Animals↗

PubMed1981

Direct effects of gram-negative endotoxin on skeletal muscle glucose uptake.

The effect of locally infused endotoxin on gracilis muscle glucose uptake was determined in anesthetized mongrel dogs. Locally infused endotoxin consistently caused an increase in skeletal muscle glucose uptake with no alterations in any other metabolic variable. These data demonstrate that endotoxin can act locally to increase glucose uptake by skeletal muscle, independent of the action of insulin or other metabolic factors. On the other hand, when endotoxin was given systemically to induce shock, gracilis muscle glucose uptake did not increase. These differences may reflect the reduction in plasma endotoxin concentration mediated by the reticuloendothelial system (RES). However, live Escherichia coli shock was associated with an increase in glucose uptake in the constant flow perfused gracilis muscle after 4.5 h of shock. We believe this increase in muscle glucose uptake resulted from the direct effects of endotoxin, the plasma concentration of which presumably increased as the RES was overwhelmed and became less effective. The contribution of this phenomenon to the hypoglycemia of gram-negative endotoxin or septic shock cannot be evaluated from this study.

Animals↗

PubMed1986

In vitro myocardial performance after lethal and nonlethal doses of endotoxin.

The present study was initiated to determine whether the myocardial effects of an in vivo injection of endotoxin into rats were correlated with the dose and thus the lethality of the endotoxin administered. All animals in this study were used 4 h after a bolus injection of 1,000, 100, 10, or 1 microgram/100 g body wt of Escherichia coli endotoxin. At this time, mean arterial blood pressure had returned to control levels but cardiac output was still depressed at the three higher doses as previously reported [Am. J. Physiol. 248 (Regulatory Integrative Comp. Physiol. 17): R471-R478, 1985]. Intrinsic function of the myocardium was assessed using the isolated perfused working heart preparation. Cardiac output and pressure development were measured at varying preloads and at two levels of aortic outflow resistance. In vitro approaches were chosen for this study to eliminate peripheral vascular changes and humoral or neural alterations that might influence myocardial performance in vivo. Results indicate that coronary vascular resistance was increased in all hearts from endotoxin-treated animals compared with controls. In addition, myocardial performance was impaired at several doses of endotoxin, and the degree of dysfunction was dependent on the dose of endotoxin administered. Dysfunction, i.e., a depression in cardiac output times peak systolic pressure, was evident at the two higher doses in which there was 50 and 10% lethality by 24 h and also in the lower dose of 10 micrograms/100 g, which was nonlethal. Cardiac output appeared to be very sensitive to the consequences of endotoxin administration. Defects in myocardial performance could be revealed by increasing preload or afterload stress on the hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Role of platelet-activating factor and eicosanoids during endotoxin-induced lung injury in pigs.

We hypothesized that platelet-activating factor (PAF) and eicosanoids might be important mediators of endotoxin-induced respiratory failure in pigs. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg the 1st h, followed by 2 micrograms.kg-1.h-1 for 3 h in the presence and absence of SRI 63-675, a specific PAF receptor antagonist. During phase I (i.e., 0-2 h), endotoxin caused pulmonary hypertension and hypoxemia, decreased cardiac index, increased pulmonary vascular resistance, and increased plasma concentrations of thromboxane B2 (TxB2), prostaglandin (PG)F2 alpha, and 6-keto-PGF1 alpha. These phase I effects were attenuated or blocked by SRI 63-675 (10 mg/kg before endotoxin + 3 mg.kg-1.h-1 during endotoxemia). During phase II endotoxemia (i.e., 2-4 h), the PAF receptor antagonist blocked endotoxin-induced pulmonary edema and hypoxemia and increased relative permeability index of the alveolar-capillary membrane. SRI 63-675 also blocked the endotoxin-induced increases in plasma and bronchoalveolar lavage fluid concentrations of leukotriene B4 (LTB4). Ex vivo stimulation of whole blood with calcium ionophore caused large increases in plasma concentrations of TxB2 and LTB4. These increases were not significantly modified in blood derived from pigs treated with SRI 63-675, indicating no inhibition of cyclooxygenase or 5-lipoxygenase and suggesting that the in vivo effects were PAF receptor mediated. We conclude that PAF plays an important role in the release of eicosanoids during endotoxemia and in mediating, either directly or indirectly, endotoxin-induced lung injury in anesthetized pigs.

Animals↗

PubMed1995

Tirilazad mesylate (U-74006F) inhibits effects of endotoxin in dogs.

The present study explored the effects of a potent antioxidant, the 21-aminosteroid U-74006F, on the systemic and regional hemodynamics and the oxygen extraction capabilities during endotoxic shock. Twenty-four anesthetized dogs were randomized into three groups. Group 1 (n = 8) served as control. Group 2 (n = 8) and group 3 (n = 8) received 2 mg/kg iv of Escherichia coli endotoxin, followed 30 min later by saline infusion. Group 3 was given U-74006F as an intravenous bolus of 80 micrograms/kg followed by an infusion of 10 micrograms.kg-1.min-1, and group 2 received an equivalent volume of vehicle. Tamponade was induced 30 min later to study the oxygen extraction capabilities of the animals. Compared with the endotoxin-alone group, the U-74006F-treated dogs maintained higher mean arterial pressure, cardiac index, stroke volume index, and left ventricular stroke work index and lower pulmonary vascular resistance. They also showed a higher fractional blood flow to mesenteric and renal beds. Endotoxin administration increased whole body critical oxygen delivery (DO2crit) from 7.7 +/- 2.4 to 12.0 +/- 1.9 ml.kg-1.min-1 (P < 0.05), but U-74006F decreased DO2crit to 7.8 +/- 2.0 ml.kg-1.min-1 (P < 0.05 vs. endotoxin alone). Endotoxin decreased critical oxygen extraction ratio (O2ERcrit) from 75.0 +/- 12.7 to 44.3 +/- 8.7% (P < 0.05), but U-74006F increased O2ERcrit to 64.1 +/- 11.2% (P < 0.05 vs. endotoxin alone). U-74006F also decreased endotoxin-induced elevation of mesenteric and renal DO2crit and markedly increased regional O2ERcrit. Systemic and regional blood lactate concentrations were lower in the U-74006F-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1976

Suppressive effect of endotoxin on erythropietin-responsive cells in mice.

Infection may be associated with failure of erythropoiesis, and endotoxin has been shown to cause a decrease in the number of erythroid cells in the marrow of mice. We have investigated the effect of endotoxin on erythropoiesis in BDF1 mice by studying its effect on the incorporation of intravenously administered 59Fe into peripheral red cells. In normal mice the injection of endotoxin 2 and 3 days prior to the administration of 59Fe results in suppression of its incorporation into red cells. In exhypoxic polycythemic mice, endotoxin suppresses the response to erythropoietin injection when the endotoxin is given prior to or at the same time as the erythropoietin. This effect is much less marked when endotoxin is given after erythropoietin. We conclude that endotoxin either 1) impairs the function of erythropoietin-responsive cells, 2) competively decreases erythroid progenitors by stimulating granulocytes, or 3) inactivates erythropoietin.

Animals↗

PubMed2003

Smooth muscle F-actin disassembly and RhoA/Rho-kinase signaling during endotoxin-induced alterations in pulmonary arterial compliance.

Endotoxemia is associated with changed pulmonary vascular function with respect to vasoreactivity, endothelial permeability, and activation of inducible nitric oxide synthase II (NOSII). However, whether altered passive arterial wall mechanics contribute to this endotoxin-induced pulmonary vascular dysfunction is still unknown. Therefore, we investigated whether endotoxin affects the passive arterial mechanics and compliance of isolated rat pulmonary arteries. Pulmonary arteries of pentobarbital-anesthetized Wistar rats (n = 55) were isolated and exposed to Escherichia coli endotoxin (50 microg/ml) for 20 h. Endotoxin increased pulmonary artery diameter and compliance (transmural pressure = 13 mmHg) in an endothelium-, Ca2+-, or NOSII-induced NO release-independent manner. Interestingly, the endotoxin-induced alterations in the passive arterial mechanics were accompanied by disassembly of the smooth muscle cell (SMC) F-actin cytoskeleton. Disassembly of F-actin by incubation of control arteries with the cytoskeleton-disrupting agent cytochalasin B or the Rho-kinase inhibitor Y-27632 induced a similar increase in passive arterial diameter and compliance. In contrast, RhoA activation by lysophosphatidic acid prevented the endotoxin-induced alterations in the pulmonary SMC F-actin cytoskeleton and passive mechanics. In conclusion, these findings indicate that disassembly of the SMC F-actin cytoskeleton and RhoA/Rho-kinase signaling act as mediators of endotoxin-induced changes in the pulmonary arterial mechanics. They imply the involvement of F-actin rearrangement and RhoA/Rho-kinase signaling in endotoxemia-induced vascular lung injury.

Actins↗

PubMed2005

Chronic endotoxin exposure does not cause sustained structural abnormalities in the fetal sheep lungs.

Chronic early gestational chorioamnionitis is associated with development of bronchopulmonary dysplasia in preterm infants. A single intra-amniotic exposure to endotoxin decreased alveolarization and reduced expression of endothelial proteins in 125-day gestational age preterm lambs. We hypothesized that prolonged exposure to intra-amniotic endotoxin would cause progressive lung inflammation and inhibit alveolar and pulmonary vascular development. Endotoxin (1 mg/day) or saline was administered via an intra-amniotic osmotic pump from 80 to 108 days of gestational age (continuous pump) or by four weekly 10-mg intra-amniotic endotoxin injections starting at 100 days of gestational age (multiple dose). Lung morphometry, lung inflammation, vascular effects, and lung maturation were measured at delivery. The continuous pump lambs delivered at 100 days (approximately 70% of total endotoxin exposure) had lung inflammation, fewer saccules, and decreased endothelial proteins endothelial nitric oxide synthase and VEGF receptor 2 expression compared with controls. The continuous pump (delivered at 138 days) and multiple dose lambs (delivered at 130 and 145 days) had mild persistent lung inflammation and no significant differences in lung morphometry or expression of endothelial proteins compared with controls. Surfactant saturated phosphatidylcholine pool sizes were increased in all endotoxin-exposed groups, but lung function was not changed relative to controls. Contrary to our hypothesis, a prolonged fetal exposure to intra-amniotic endotoxin caused mild persistent inflammation but did not lead to progressive structural abnormalities in lungs of near-term gestation lambs.

Amniotic Fluid↗

PubMed1989

Endotoxin increases lung Cu,Zn superoxide dismutase mRNA: O2 raises enzyme synthesis.

Administration of endotoxin to adult rats increases lung Cu,Zn superoxide activity after 72 h of exposure to greater than 95% O2. The increased activity is brought about mainly by a faster rate of Cu,Zn superoxide dismutase synthesis; rats treated with endotoxin but not exposed to hyperoxia do not exhibit these findings (Hass, Frank, and Massaro, J. Biol. Chem. 257: 9379-9383, 1982). We now report that 48 h after treatment of adult rats with endotoxin there was a decreased rate of Cu,Zn superoxide dismutase synthesis by lung slices from air- and O2- exposed rats, although, in both groups, the lung concentration of Cu,Zn superoxide dismutase mRNA was increased approximately 45%. Exposure of endotoxin-treated rats to greater than 95% O2 or air for an additional 24 h (72 h all told) resulted in continued elevation of Cu,Zn superoxide dismutase mRNA only in lungs of O2- exposed rats. In vitro exposure of lung slices from air-breathing saline- or endotoxin-treated rats to 95% O2 for 6 h led to an increased rate of Cu,Zn superoxide dismutase synthesis only in slices from endotoxin-treated rats. We conclude that endotoxin treatment leads to an increased concentration of Cu,Zn superoxide dismutase mRNA in rat lungs, but a sustained elevation of the mRNA, and its translation into an increased rate of Cu,Zn superoxide dismutase synthesis requires exposure of the lung to hyperoxia.

Animals↗