Lung Retention Research Articles

Ventilation with positive end-expiratory airway pressure causes leukocyte retention in human lung.

We examined the effect of assisted ventilation with different positive end-expiratory airway pressures (PEEP) on pulmonary leukocyte retention in humans after cardiopulmonary bypass. Eight patients who underwent heart surgery were ventilated in the postoperative phase briefly with 10 (39.6 +/- 0.9 s) and 20 cmH2O (40.3 +/- 1.0 s) PEEP. Before, during, and after this ventilatory maneuver, blood was withdrawn simultaneously from catheters placed in the pulmonary and radial arteries for blood cell differentials. At the same time points, pulmonary and systemic hemodynamics were recorded. During PEEP ventilation, there was a four- (10 cmH2O PEEP) and an eightfold (20 cmH2O PEEP) increase in mixed venous-arterial leukocyte cell difference compared with baseline. This phenomenon was based mainly on a transpulmonary cell difference of polymorphonuclear cells. Likewise, the lymphocytes were entrapped in the pulmonary vasculature during PEEP ventilation. During the ventilatory maneuver, the pulmonary blood flow was significantly reduced; it was indexed by a declined cardiac output. We conclude that PEEP ventilation in the post-operative phase after cardiopulmonary bypass causes pulmonary polymorphonuclear cell entrapment. The most likely mechanism for this phenomenon is the compression of alveolar capillaries and reduced pulmonary blood flow in response to the raised alveolar pressure.

Mucociliary clearance of inhaled particles measured at 2 h after ozone exposure in humans

Acute exposure of humans to ozone is known to acutely cause pulmonary function decrements, inflammation, and increased permeability of pulmonary epithelium. A single study in humans has also shown that mucociliary transport increases during acute ozone exposure. Because different responses have shown a different time course of recovery after exposure, it was important to examine mucociliary transport at a different time after the cessation of ozone exposure. We exposed 15 healthy male and female nonsmoking subjects, on different occasions, to clean air and 0.4 ppm ozone for 1 h while they exercised continuously. Pulmonary function was measured immediately before and after exposure and 90 min and 24 h after exposure. Between 2 and 5 h after each exposure, retention of inhaled 5-microns mass median aerodynamic diameter 99mTc-labeled Fe2O3 particles was measured. Each subject returned the next day for a final particle retention measurement. Despite significant changes in pulmonary function, there was no difference in mean whole lung retention time of particles between clean air [77.9 +/- 0.8 (SE) min] and ozone (78.0 +/- 0.8 min) exposures, indicating that mucociliary transport is unaffected by ozone exposure when it is measured 2 h after exposure.

Lung retention of phosphatidylcholine and cholesterol from liposomes: effects of oxygen exposure and fasting.

Antioxidants such as glutathione may play a role in prevention and treatment of several lung diseases. Liposomes can be used to deliver antioxidants to the lung and increase their retention. In addition, liposomes alone may protect against oxidant-induced damage. In addition, liposomes alone may protect against oxidant-induced damage. This study was designed to characterize the retention and distribution of liposomes in the lung under normal circumstances and during either fasting, exposure to 100% oxygen, or a combination of the two. Positively charged liposomes, consisting of phosphatidylcholine (PC), cholesterol, and stearylamine plus either [14C]cholesterol or [3H]PC, were instilled intratracheally. Five minutes to 5 days later the lungs were removed and the radioactivity determined. Both [14C]cholesterol and [3H]PC labels had prolonged and equal retention in the lung, but their distribution within lung compartments differed. The cholesterol label increased in lung tissue over time, comprising 78% of the remaining label after 5 days, whereas the PC label persisted at high levels in lavage fluid and became equally distributed between lung tissue and bronchoalveolar lavage fluid. Fasting had little effect on the retention of the labels and no effect on their distribution within the lung. Exposure to 100% oxygen increased lung retention of both radiolabels and altered their distribution such that [14C]cholesterol label decreased and [3H]PC label increased in lung tissue. These results demonstrate the prolonged retention of intratracheally administered liposomes or their components in the lung and the effects of two clinically relevant conditions, fasting and hyperoxic exposure. Furthermore, they provide a basis for designing future studies using liposomes.

Enhancement of Metastatic Potential of Murine and Human Melanoma Cells by Laminin Receptor Peptide G: Attachment of Cancer Cells to Subendothelial Matrix as a Pathway for Hematogenous Metastasis

Stable anchorage of circulating cancer cells to the vasculature is a critical step in the formation of hematogenous metastases. Although the basement membrane glycoprotein laminin clearly plays a crucial role in this event, the exact interactive pathways among cancer cells, laminin, and the vessel wall have not been elucidated. In a previous study, we identified synthetic peptide G, which contains the laminin-binding domain of the 67-kd laminin receptor and which inhibits tumor cell adhesion to endothelial cells. To assess the role of the interaction between laminin and the 67-kd laminin receptor in hematogenous metastasis formation, we studied the effect of peptide G on melanoma cell behavior in vivo and in vitro. The effect of peptide G and control peptides was studied in vivo on lung retention and colonizing potential of murine (B16BL6) and human (A2058) melanoma cells injected intravenously in C57BL/6 and nude mice, respectively. In addition, their effect on cell adhesion and chemotaxis to laminin and on binding of iodine 125-labeled laminin to cells was studied in vitro. In vivo, pretreatment of cells with peptide G resulted in a two- to 10-fold significant increase in the number of experimental lung metastases. A significant relative increase in lung retention of peptide G-treated tumor cells was observed 48 hours after injection, although after 4 hours a partial reduction was observed. In vitro, peptide G significantly increased laminin binding and cancer cell adhesion to laminin and subendothelial matrix, whereas chemotaxis to laminin was significantly inhibited. Peptide G differentially affected the biological response of cancer cells to laminin. In vitro, it increased laminin binding and cell adhesion to laminin and subendothelial matrix, whereas it inhibited cell chemotaxis to laminin. In vivo, the overall effect of peptide G was an augmentation of lung metastasis. Our findings suggest that direct adhesion of tumor cells to the subendothelial matrix is a main pathway for hematogenous metastases and that tumor cell-matrix interaction may be more relevant than tumor cell-endothelial cell attachment in this process.

Lung clearance in Long-Evans rats after inhalation of porous, monodisperse cobalt oxide particles.

Lung clearance of a well-defined uniform and respirable material was conducted to aid in the development of models used to relate inhalation of inorganic hazardous particles to organ doses and bioassay measurements, and in particular to aid in the extrapolation of animal data to humans. In the present study, lung clearance was investigated in Long-Evans rats using monodisperse, porous, 0.8- and 1.7-microns-diameter cobalt oxide (Co3O4) test particles. An advanced inhalation technique for rats using endotracheal intubation yielded exclusive particle deposition in the pulmonary region without external pelt contamination, thus allowing for clearance studies starting directly after inhalation. The kinetics of lung clearance was distinguished between the two dominant clearance mechanisms of mechanical particle transport to the larynx and translocation of dissolved particle material to blood. A particle fraction of about 40% was cleared by short-term particle transport to the larynx, both the long-term particle transport rate and the translocation rate of dissolved particle material given as fractional rates of the retained particle mass in the lungs were not constant with time. The former declined from 0.03 to 0.004 d-1 during 6 months after inhalation. The latter depended on the specific surface area of the porous particles and increased with time from 0.08 and 0.04 d-1 for 0.8- and 1.7-microns particles, respectively. The results obtained were compared to previously reported data obtained from Fischer-344 rats and HMT rats. These were part of a previously reported interspecies comparison of lung clearance followed in seven species, including humans, and using the same batches of Co3O4 test particles. Long-term lung retention was similar in Long-Evans rats and HMT rats but decreased faster for both particle sizes than in Fischer-344 rats, as a result of a significantly faster translocation of dissolved material from the test particles to blood. Mechanical particle transport to the larynx was comparable in all three species.

Effect of Bronchopulmonary Lavage on Lung Retention and Clearance of Particulate Material in Hamsters

Effect of Bronchopulmonary Lavage on Lung Retention and Clearance of Particulate Material in Hamsters

Effect of bronchopulmonary lavage on lung retention and clearance of particulate material in hamsters.

Hamsters were exposed to an aerosol of fused aluminosilicate particles (FAP) labeled with 57Co. Three groups of animals were given bronchopulmonary lavage, beginning at either 1 week, 1 month, or 6 months after exposure. Each treated group was lavaged eight times over a period of 25 days. Each lavage involved 10 saline washes of the lungs. For each group, about 60-70% of the body content of 57Co at the start of lavage treatment was removed; nearly half of this was recovered in the first two lavages. A positive correlation was demonstrated between the macrophage content and 57Co activity of the washings. The subsequent fractional clearance rate of 57Co from lavaged animals was not significantly different from that in a group of untreated control animals.

Comparison of Lung Carcinoma Incidence in Beagle Dogs Exposed to 239PuO2 as Young Adults or as Immature Dogs

Beagle dogs were exposed by inhalation either as immature ("3 months of age) or as young adult (" 13 months of age) dogs to monodisperse particles of 239PuO2. These particles are relatively insoluble in vivo and thus the majority of the radiation dose is delivered to the lung and associated tissues. As have been reported previously there were no apparent differences in lung retention associated with age at exposure. Time-dependent radiation doses to the lung, averaged over the total lung mass, were calculated to take into account the growing lung of the immature dog. There were 108 immature dogs exposed to a monodisperse 1.5 µm AMAD particles (74 survivors are 7-10 years after exposure) and 252 young adults dogs exposed to 0.75, 1.5 or 3.0 µm AMAD particles (52 survivors are 11-13 years after exposure). To date, 24 immature dogs have died with lung carcinomas at doses of 2.5 to 83 Gy and 104 young adult dogs have died with lung carcinomas at doses of 3.2 to 89 Gy. The lung carcinoma incidence rates for the two study groups were compared using a Cox proportional hazards model with a time-dependent dose. A common baseline incidence rate was used so that risks would be estimated relative to the same baseline. No statistically significant difference (P>0.30) was found between the immature and the young adult dogs in how their lung carcinoma incidence rates increased with radiation dose. This suggests that there is not a unique radiosensitivity attributable to alpha particle irradiation of a growing lung.

Pulmonary retention of ultrafine and fine particles in rats.

In aerosol research, particle size has been mainly considered in the context of the role it plays in particle deposition along the respiratory tract. The possibility that the primary particle size may affect the fate of particles after they are deposited was explored in this study. Rats were exposed for 12 wk to aerosolized ultrafine (integral of 21 nm diameter) or fine (integral of 250 nm diameter) titanium dioxide (TiO2) particles. Other rats were exposed to TiO2 particles of various sizes (12, 21, 230, and 250 nm) by intratracheal instillation. After the rat lungs were extensively lavaged, analysis of particle content in the lavaged lungs, lavage fluid, and of lymphatic nodes was performed. Electron and light microscopy was also performed using unlavaged lungs. Both acute instillation and subchronic inhalation studies showed that ultrafine particles (integral of 20 nm) at equivalent masses access the pulmonary interstitium to a larger extent than fine particles (integral of 250 nm). An increasing dose in terms of particle numbers and a decreasing particle size promoted particle access into the interstitium. The translocation of particles into the interstitium appeared to be a function of the number of particles, and the process appeared to be related to the particle size, the delivered dose, and the delivered dose rate. A net effect of the preferential translocation of the smaller particles into the interstitium was a prolongation in their lung retention. After the 12-wk inhalation exposure, pulmonary clearance of ultrafine particles was slower (t1/2 = 501 days) than of larger particles (t1/2 = 174 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Glutathione Localization and Distribution after Intratracheal Instillation: Implications for Treatment

To gain insight into how glutathione given directly into the lung protects fasted mice against hyperoxic lung damage and to provide a framework for developing treatment strategies in patients, we determined the lung distribution and retention of intratracheally administered glutathione (GSH) and its fate after leaving the lung. Mice received an intratracheal injection of [3H]GSH with or without cold GSH and with or without liposomes. The distribution of the 3H label was equal in both lungs, but the left lung had a higher concentration because of its smaller size. The 3H label was cleared rapidly from the lung: only 1% remained at 24 h, and more than 50% of the label at that time was no longer attached to the GSH. Administration of GSH with liposomes increased the retention of GSH by 20 to 50%, but the amount remaining at 24 h was still only 1%. The increase associated with the liposomes was due to enhanced retention of the GSH encapsulated in the liposomes, not the much larger amount present free in the GSH-liposome mixture. Fasting and exposure to 100% oxygen had little effect on GSH retention. Some of the 3H label leaving the lung was excreted by the kidneys, a small amount was retained in the liver, and a large amount accumulated in the blood. Of the amount in the blood, about 60% was in red blood cells (RBC) and the rest in plasma. Much of the 3H label in RBC and lung at 24 h was no longer attached to the GSH, whereas most in the plasma and liver was.(ABSTRACT TRUNCATED AT 250 WORDS)

Mucus clearance at rest and during exercise in patients with bronchial hypersecretion

The purpose of this study was to measure the effects on mucus clearance after physical exercise. We measured mucociliary clearance at rest and during exercise in eleven patients with mild or moderate bronchial hypersecretion. The subjects inhaled an aerosol containing 99mTc-labelled albumin millimicrospheres. Four sets of scintigraphic images were obtained with 15 minute intervals. The lung retention of radioactivity was quantified using a gamma camera and the clearance of particles from the lungs were calculated for each 15 min period. The first image was obtained directly after inhalation, the second after a period of 15 min rest, the third after a period of exercise on a bicycle ergometer and the final fourth image after another period of rest. We found no differences in the clearance rate at rest and after exercise.

Using animal dosimetry models to interpret human bioassay data for actinide exposures

Bioassay and dosometry models are needed to estimate intakes of radionuclides, and to calculate radiation doses to target tissues following such in takes. Because of the diversity of exposure materials, individual biological variabilities, and the general lack of adequate bioassay information and knowledge of the metabolism of radionuclides, current models are based mostly on empiricism. This paper describes biokinetic/dosimetry models for U, Am, and Cm. They are based on experimental data developed from studies in dogs that inhaled one of the above radionuclides in specific chemical forms and specific particle sizes. The models, which are based on similar biological principles, and, therefore, have similar structure, are applied to the very sparse human bioassay data available from cases of exposure to either U, Am, or Cm. The results thus far indicate that the lung retention for the different actinides are well described by the models, that urinary bioassay data can be described within limited time periods, and that the fecal excretion rate is not adequately described. Improvements in modeling are predicted on increased publication of human bioassay data, and better cooperative interaction between model developers and health protection professionals responsible for industrial bioassay programs.

Volumetric loading of alveolar macrophages (AM): a possible basis for diminished AM-mediated particle clearance.

Using intratracheal instillation of radioactively labeled plastic microspheres of 3.3 and 10.3 microns diameter at two dose levels, this 7-month study in male Fischer 344 rats was designed to test a volumetric particulate burden hypothesis that has been proposed as a mechanistic basis for the condition of dust overloading of the lungs with highly insoluble particles of very low toxicity and to explain the prolongation of pulmonary particle retention. The study utilized airway and deep lung lavage techniques, scanning electron and optical microscopy of lavaged cells and lungs of sacrificed animals, particle distribution in alveolar macrophages (AM), fecal recovery of radioactive particles, and lung retention measurements by external counting. Microscopic assessments revealed that essentially all of the 3.3- and 10.3-microns-diameter particles were phagocytized by AM within 24 h postinstillation. One phagocytized 10.3-microns particle is capable of producing the hypothesized 600-microns 3/AM overload criterion for virtual AM immobilization. Neither the number nor the volume of 3.3-microns-diameter particles instilled was large enough to produce volumetric overloading assuming uniform distribution of the particles in the lung. In contrast to the 3.3-microns particles, the 10.3-microns particles were apparently sequestered to a greater extent and capable of greatly prolonging AM-mediated clearance of particles from the pulmonary region. The measured pulmonary retention half-times for the small and large particles were 86-109 days and 870-1020 days, respectively. Fecal recovery data closely complemented pulmonary clearance data for both particle sizes. The two-particle approach was found supportive of the volumetric overload hypothesis.

Regional deposition of 3.6-micron particles and lung function in asthmatic subjects

In a group of moderately severe asthmatic subjects, regional deposition of 3.6-microns (aerodynamic diameter) monodispersed Teflon particles labeled with 111In was studied twice. The particles were inhaled with maximally deep inhalation at 0.5 l/s. Lung retention was measured at 0, 6, 24, and 48 h by use of a profile scanner equipped with two 13 x 5-cm NaI crystals. The retentions at 24 (Ret24) and 48 h were highly correlated (r = 0.96 with a slope of the regression line close to 1). There was a poor correlation between retention at 6 h and Ret24 (r = 0.54). The Ret24 values at the two exposures were well correlated (r = 0.86). There were significant correlations between airway resistance as well as single-breath nitrogen test phase III and Ret24 (r = 0.70 and 0.67, respectively). The correlation between single-breath nitrogen test phase III and Ret24 persisted also when only subjects within a narrow interval of airway resistance were included. The study indicates that regional deposition can be studied by measurements of Ret24 in subjects with moderately severe asthma and that it is dependent on changes in both large and small airways.

Effects of varying marijuana smoking profile on deposition of tar and absorption of CO and delta-9-THC

We investigated the effects of previously observed differences in smoking technique for marijuana (M) versus tobacco (T) on the amount of inhaled tar, the percentage retention of inhaled tar in the lung, the pre- to postcigarette boost in blood carboxy-hemoglobin (COHb) and in serum delta-9-tetrahydrocannabinol (THC concentrations), and psychophysiologic responses to THC (increased heart rate and subjective “high”). Ten healthy, habitual smokers of M were studied on 6 separate days. On each day, subjects smoked a single M cigarette (∼900 mg, 1.24% delta-9-THC) using one of 6 different smoking profiles typical for marijuana [puff volume (PV) ∼70 ml; breathholding time, (BHT) 14–16s] or tobacco (PV ∼ ml; BHT 4–5 s) or a combination of the two techniques (PV ∼70 ml and BHT 4–5 s; or PV ∼45 ml and BHT 14–16s). Inhaled volume (1.5 liters), interpuff interval (30 s) and number of puffs (6) were all fixed, except that for the ∼45-ml PV condition, the number of puffs was increased to 10 in 2 additional sessions to standardize the total amount of cigarette consumed to that of the ∼70 ml PV condition. The longer BHT significantly increased both percent retention of tar in the lung and the pre- to postsmoking rise in blood COHb, serum THC and heart rate, independent of puff volume and number. In contrast, the larger PV had no significant influence on these variables for the same amount of cigarette consumed. The longer BHT (and not the larger PV) characteristics of M smoking contributes to the greater COHb boost and lung retention of inhaled tar during M compared to T smoking. In addition, the longer BHT appears to enhance THC absorption.

Lung clearance and retention of toner, utilizing a tracer technique, during chronic inhalation exposure in rats

Male and female F-344 rats were exposed 6 hr/day, 5 days/week for up to 24 months to a special test toner at 0, 1, 4, and 16 mg/m 3, TiO 2 at 5 mg/m 3, or SiO 2 at 1 mg/m 3 by the inhalation route. 59Fe-labeled iron oxide and 85Sr-labeled polystyrene particles were periodically inhaled by the nose-only route and used to measure alveolar clearance rates during the course of the study. This method was used to describe a maximum functionally tolerated dose (MFTD). Pulmonary retention of toner and control materials (TiO 2 and SiO 2) was measured after 3, 9, 15, 21, and 24 months of exposure. The quantity of all three materials retained in the lungs and lung-associated lymph nodes increased with exposure duration and level. The final pulmonary burdens of toner at the three exposure levels were 0.22, 1.73, and 15.6 mg/lung, respectively. Alveolar clearance of both tracers was substantially impaired at the toner high-exposure level, and moderately slowed at the toner middle-exposure level. The excessive quantity of toner retained and the substantially retarded clearance in the toner high-exposure group are indicative of “lung overloading.” Alveolar clearance of 85Sr-polystyrene particles was slightly slowed in the TiO 2-exposed group and substantially impaired in the SiO 2-exposed group. The alveolar clearance of the unexposed rats decreased about 30% during the study, a change ascribed to aging. For a general description of the toxicokinetics of the various dusts, a semiempirical kinetic model was developed, which could generally be useful for the extrapolation of lung retention of insoluble particles from a subchronic to a chronic inhalation study. Both the maximum tolerated dose (MTD) and the MFTD were exceeded at the toner high-exposure level during the study in rats.

Lung Clearance and Retention of Toner, Utilizing a Tracer Technique, during Chronic Inhalation Exposure in Rats

Lung Clearance and Retention of Toner, Utilizing a Tracer Technique, during Chronic Inhalation Exposure in Rats. Bellmann, B., Muhle, H., Creutzenberg, O., Dasenbrock, C., Kilpper, R., MacKenzie, J. C., Morrow, P., and Mermelstein, R. Fundum. Appl. Toxicol. 17, 300–313. Male and female F-344 rats were exposed 6 hr/day, 5 days/week for up to 24 months to a special test toner at 0, 1, 4, and 16 mg/m3, TiO2 at 5 mg/m3, or SiO2 at 1 mg/m3 by the inhalation route. 59Fe-labeled iron oxide and 85Sr-labeled polystyrene particles were periodically inhaled by the nose-only route and used to measure alveolar clearance rates during the course of the study. This method was used to describe a maximum functionally tolerated dose (MFTD). Pulmonary retention of toner and control materials (TiO2 and SiO2) was measured after 3, 9, 15, 21, and 24 months of exposure. The quantity of all three materials retained in the lungs and lung-associated lymph nodes increased with exposure duration and level. The final pulmonary burdens of toner at the three exposure levels were 0.22, 1.73, and 15.6 mg/lung, respactively. Alveolar clearana of both tracers was substantially impaired at the toner high-exposure level, and moderately slowed at the toner middle-exposure level. The excessive quantity of toner retained and the substantially retarded clearance in the toner high-exposure group are indicative of “lung overloding.” Alveolar dearance of 85Sr-polystyrene particles was slightly slowd in the TiO2-exposed group and substantmlly impaired in the SiO2-exposed group. The alveolar clearance of the unexposed rats decreased about 30% during the study, a change ascribed to aging For a general description of the toxicokinetics of the various dusts, a semiempirical kinetic model was developed, which could generally be useful for the extrapolation of lung retention of insoluble particles from a subchronic to a chronic inhalation study. Both the maximum tolerated dose (MTD) and the MFTD were exceedes at the toner high-exposure level during the study in rats.

Interspecies comparison of lung clearance after inhalation of monodisperse, solid cobalt oxide aerosol particles

An interspecies comparison of the lung clearance of a well-defined inhalable material was conducted to aid in the development of models used to relate inhalation of radioactive particles to organ doses and bioassay measurements, and in particular to aid in the extrapolation of animal data to man. It complements a previous interspecies comparison in which lung clearance of monodisperse, porous 0.8 μm and 1.7 μm diameter cobalt oxide (Co 3O 4) particles was followed in seven species including man (Bailey et al., J. Aerosol Sci. 20, 169–188, 1989). In the present study baboons, dogs and HMT rats were used since they had shown the most prominent differences in clearance in the previous investigation. Additionally, clearance in the human volunteers and baboons was very similar. The material selected consisted of almost solid, monodisperse 0.9 μm diameter CoP 3O 4 particles which were chemically similar to the materials studied previously but differed physically with a higher density and a smaller specific surface area. Lung retention and excretion of 57Co were followed for at least six months after inhalation. Lung retention at 6 months after inhalation ranged from 60% of the initial lung deposit in baboons to 5%, in rats and in all three species clearance was considerably slower than that of porous 0.8 μm Co 3O 4 particles. Lung clearance rates due to translocation of dissociated 57Co to the blood, S( t), and due to particle transport to the GI tract M( t) were calculated. Initially, S( t) ranged from 0.1% of the contemporary lung content day −1 in baboons to 0.7% in rats. Depending on the initial translocation rates of each species, S( t) over time followed patterns expected from a model of particle dissolution derived previously. For each species, a correlation was found between the initial translocation rates and the specific surface area of the three particles used. Estimated values of M( t) were consistent with values obtained previously with other materials.

The lung clearance kinetics of 57Co 3O 4 in rats of various ages

The lung retention of inhaled 57Co labelled Co 3O 4 particles was measured in rats whose ages at exposure ranged from 3 to 46 weeks. Significantly lower lung retention was found in the younger animals and this could be attributed to a faster rate of translocation of 5Co from the lung to blood. Mechanical clearance rates were similar for all age groups. Comparison of these results with those of other studies suggest that mechanical clearance rates are independent of the chemical form of the material inhaled. The results of this study suggest that in the extrapolation of the results of animal experiments to humans, due consideration should be given to age related changes.

Increased vitamin E content in the lung after ozone exposure: A possible mobilization in response to oxidative stress

Vitamin E (vE) is a biological free radical scavenger capable of providing antioxidant protection depending upon its tissue content. In previous studies, we observed that vE increased significantly in rat lungs after oxidant exposure, and we postulated that vE may be mobilized to the lung from other body sites under oxidative stress. To test this hypothesis, we fed Long-Evans rats either a vE-supplemented or a vE-deficient diet, injected them intraperitoneally with 14C-labeled vE, and then exposed half of each group to 0.5 ppm ozone (O 3) for 5 days. After exposure, we determined vE content and label retention in lungs, liver, kidney, heart, brain, plasma, and white adipose tissue. Tissue vE content of all tissues generally reflected the dietary level, but labeled vE retention in all tissues was inversely related to tissue content, possibly reflecting a saturation of existing vE receptor sites in supplemented rats. Following O 3 exposure, lung vE content increased significantly in supplemented rats and decreased in deficient rats, but the decrease was not statistically significant, and vE content remained unchanged in all other tissues of both dietary groups. Retention of 14C-labeled vE increased in all tissues of O 3-exposed rats of both dietary groups, except in vE-deficient adipose tissue and vE-supplemented brain, where it decreased, and plasma, where it did not change. The marked increases in lung vE content and labeled vE retention of O 3-exposed vE-supplemented rats support our hypothesis that vE may be mobilized to the lung in response to oxidative stress, providing that the vitamin is sufficiently available in other body sites.