Biomedical subjects

J N Finkelstein

Publications and source records attributed to J N Finkelstein.

At least 55 records · Page 3Linked to original sources

PubMed1995

Vascular endothelial growth factor mRNA increases in alveolar epithelial cells during recovery from oxygen injury.

Destruction of pulmonary endothelial cells is characteristic of hyperoxic lung injury. During recovery from hyperoxia, pulmonary endothelial cells proliferate to regenerate the vascular endothelium. Vascular endothelial growth factor (VEGF) is a peptide growth factor that is mitogenic specifically for endothelial cells. We hypothesized that VEGF messenger RNA (mRNA) increases during recovery from acute hyperoxic lung injury. Adult rabbits were exposed to 100% oxygen for 64 h and allowed to recover in air for 0, 1, 3, and 5 days. In situ hybridization showed increased VEGF expression in alveolar epithelial cells beginning at 1 day recovery. By 3 days recovery the message was in alveolar epithelial cells throughout the lung. Compared with alveolar epithelial cells, little or no expression was noted in large vessel endothelial cells, airway cells, or smooth muscle cells. Combined in situ hybridization for VEGF and immunostaining for macrophages and other mesenchymal cells found no VEGF message in those cell types. Isolated alveolar macrophages had no detectable VEGF message. Cells expressing VEGF mRNA were enriched in alveolar type II cell preparations from recovering lung. Double in situ hybridization for VEGF and surfactant protein-C (SP-C) showed co-expression in a population of type II cells, but with an inverse relationship: cells with abundant VEGF mRNA did not have abundant SP-C mRNA. Type II cells in vitro expressed VEGF message, but only when the SP-C message abundance was relatively low. We conclude that alveolar type II cells express increased VEGF mRNA during recovery from acute hyperoxia. These findings are consistent with a role for VEGF in regulating microvascular endothelial repair after oxidant injury.

Animals↗

PubMed1995

Cell-specific expression of fibronectin in adult and developing rabbit lung.

Fibronectin (FN), a glycoprotein component of the extracellular matrix, plays a role in tissue morphogenesis and tissue-specific differentiation through its effects on cell adhesion, cell shape, and cytoskeletal organization. Immunohistochemistry has been used to show that during lung development FN deposition changes, yet the cell-specific sites of pulmonary FN synthesis have not been determined. Because cellular FN synthesis is reflected by FN mRNA abundance, we performed in situ hybridizations to identify pulmonary tissue with the capacity to synthesize FN. Both in situ mRNA hybridization and immunohistochemical staining were performed on tissue sections from lungs of adults and late gestation fetal and neonatal rabbits. In adults, FN transcripts and immunostaining were clearly seen in endothelial cells, smooth muscle cells, and chondrocytes. During lung development, FN transcripts were virtually ubiquitous except in airway epithelium. There was a gradual decrease in FN mRNA abundance with advancing fetal age, but low levels of FN mRNA persisted in neonatal and adult lungs. In contrast, parenchymal immunostaining increased throughout fetal development and remained elevated in the newborn. FN immunostaining was lower in adult lung. In all tissues examined, airway epithelial cells contained no FN transcripts above background. However, immunostaining was detected in airway basement membrane zones and on luminal surfaces of some epithelial cells. The lack of FN transcripts in airway epithelial cells suggests that FN synthesis does not normally occur in this cell type and that its associated FN immunostaining is from another source. The colocalization of FN mRNA and protein in pulmonary endothelial cells, smooth muscle cells, and chondrocytes in adults strongly suggests that these cells are sites of FN synthesis.

Animals↗

PubMed1995

Secretion of transforming growth factor-alpha (TGF alpha) by postnatal rabbit alveolar macrophages.

Transforming growth factor-alpha (TGF alpha) is a cytokine secreted by stimulated alveolar macrophages (AM) in vitro and after in vivo particulate or hyperoxia exposure and has been implicated in the processes of postnatal lung development. It is unknown if AM TGF alpha secretion changes during normal postnatal lung development. After sacrifice of New Zealand white rabbits on postnatal d 0-2, 5-7, 9-10, 14, 21, and 28 and > 4 mo (adult), AM were isolated by discontinuous density centrifugation and placed in culture in the presence or absence of concanavalin A (ConA) for 24 h. Media were collected, and the concentration and isoforms of TGF alpha in AM media samples were determined by an epidermal growth factor/TGF alpha radioreceptor assay and Western immunodetection, respectively. TGF alpha was present in media of AM from the 1.06 and 1.08 g/dL Percoll densities, but not in the 1.10 g/dL density. Statistically significant differences in TGF alpha secretion by unstimulated and ConA-stimulated AM at the various ages were not detected until d 14 (p < 0.02). Western blot analysis of unstimulated AM media samples from d 0-7 rabbits demonstrated the presence of TGF alpha isoforms at 46, 30, and 14.3 kD. At later postnatal ages (> or = d 9), a single 14.3-kD isoform was present. In contrast, analysis of ConA-stimulated AM media samples showed TGF alpha isoforms at 46, 30, and 14.3 kD for all ages; however, the 6-kD mature isoform was present only in juvenile (d 28) and adult media.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1995

Differences in correlation of mRNA gene expression in mice sensitive and resistant to radiation-induced pulmonary fibrosis.

Fibrosis, characterized by the accumulation of collagen, is a late result of thoracic irradiation. The purpose of this study was to determine if extracellular matrix protein and transforming growth factor beta mRNA expression are altered late in the course of pulmonary fibrosis after irradiation, and then to determine if these changes differ between two strains of mice which vary in their sensitivity to radiation. Radiation-sensitive (C57BL/6) and radiation-resistant (C3H/HeJ) mice were irradiated with a single dose of 5 or 12.5 Gy to the thorax. Total lung RNA was prepared and immobilized by Northern and slot blotting and hybridized with radiolabeled cDNA probes for collagens I, III and IV, fibronectin, and transforming growth factor beta 1 and beta 3. Autoradiographic data were quantified by video densitometry and results normalized to a control probe encoding for glyceraldehyde-3-phosphate dehydrogenase. Alterations in mRNA abundance were observed in the sensitive mice at all times, while levels in the resistant mice were unaffected until 26 weeks after irradiation. The relationship between extracellular matrix protein per se and increased mRNA abundance suggests that late matrix protein accumulation may be a function of gene expression. Differences in levels of transforming growth factor beta mRNA may lead to strain-dependent variation in fibrotic response and may also contribute to the radiation-induced component of pulmonary fibrosis.

Animals↗

PubMed1994

Early alterations in extracellular matrix and transforming growth factor beta gene expression in mouse lung indicative of late radiation fibrosis.

PURPOSE: Fibrosis, characterized by the accumulation of collagen, is a late result of thoracic irradiation. The expression of late radiation injury can be found immediately after irradiation by measuring messenger RNA (mRNA) abundance. METHODS AND MATERIALS: To determine if extracellular matrix mRNA and transforming growth factor beta abundance was affected acutely after irradiation, we measured mRNA levels of collagen I (CI), collagen III (CIII), collagen IV (CIV), fibronectin (FN), and transforming growth factor beta (TGF beta 1,2&3) in mouse lungs on day 1 and day 14 after graded doses of radiation. C57BL/6 female mice were irradiated with a single dose to the thorax of 5 or 12.5 Gy. Total lung RNA was prepared and immobilized by Northern and slot blotting and hybridized with radiolabelled cDNA probes for CI, CIII, CIV, FN, TGF beta 1,2&3 and a control probe encoding for glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Autoradiographic data were quantified by video densitometry and results normalized to GAPDH. RESULTS: Changes in the expression of CI, CIII, CIV, FN and TGF beta 1,2&3 were observed as early as 1 day after exposure. Through 14 days, changes in mRNA up to 5-fold were seen for any one dose. Dose related changes as high as 10-fold were also evident. The CI:CIII ratio increased gradually for the 5 Gy dose at 14 days postirradiation while the CI:CII ratio for the 12.5 Gy dose decreased by approximately 4-fold as compared to the control. CONCLUSION: These studies suggest that alterations in expression of extracellular matrix and TGF beta mRNA occur very early after radiation injury even at low doses and may play a role in the development of chronic fibrosis.

Animals↗

PubMed1994

Growth factors alter neonatal type II alveolar epithelial cell proliferation.

The type II alveolar epithelial cell plays a critical role in the repair of lung injury by repopulating the entire damaged alveolar epithelium. We report our studies of the effects of known growth factors on the in vitro proliferation of isolated neonatal rabbit type II cells. Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) increased [3H]thymidine incorporation, cell number, and labeling index above control. Transforming growth factor-beta (TGF-beta) decreased [3H]thymidine incorporation, cell number, and labeling index compared with control. When added simultaneously, TGF-beta blocked the stimulatory effect of TGF-alpha or EGF. If TGF-alpha is added before TGF-beta, the ability of TGF-beta to block the mitogenic effect of TGF-alpha was diminished the later in time TGF-beta was added. If TGF-beta was added first, later addition of TGF-alpha had no effect. The current work demonstrates that specific growth factors, including some known to be produced by other lung cells, alter the proliferation in vitro of isolated neonatal rabbit type II alveolar epithelial cells.

Animals↗

PubMed1994

Tyrosine kinase activity is necessary for growth factor-stimulated rabbit type II pneumocyte proliferation.

Tyrosine kinases are important in the signal transduction of a number of growth factors. As shown previously, transforming growth factor (TGF)-alpha stimulated proliferation of type II cells in vitro. The mitogenic effect of TGF-alpha could be blocked by the addition of the tyrosine kinase inhibitors genistein or tyrphostin. Tyrosine phosphorylation in type II cells exposed to growth factors was examined using an antiphosphotyrosine antibody. After addition of TGF-alpha, phosphorylation of a tyrosine protein with a molecular mass of 170 kD, presumed to be the epidermal growth factor receptor (EGF-R), peaked by 5 min, returning to baseline by 30 min. As expected, genistein or tyrphostin decreased the TGF-alpha-induced phosphorylation of the EGF-R. Addition of TGF-beta resulted in no newly phosphorylated tyrosine proteins. TGF-beta decreased the TGF-alpha-induced phosphorylation of the EGF-R. Previous work has shown that TGF-beta blocks the TGF-alpha stimulation of type II cell proliferation. It appears that TGF-beta interferes with TGF-alpha-induced phosphorylation of the EGF-R.

Adenocarcinoma↗

PubMed1994

Time course of postnatal lead-induced changes in dopamine receptors and their relationship to changes in dopamine sensitivity.

Although alterations in dopaminergic function represent a potential neurochemical basis of Pb-induced behavioral deficits, the impact of postnatal Pb exposure on DA systems has not been adequately delineated. This study examined the effects of postnatal Pb exposure, across a broad range of concentrations, on the ontogeny of both D1 and D2 DA (dopamine) receptors in striatum and nucleus accumbens. Rat pups were exposed to Pb from 0-21 days of age via lactating dams consuming solutions of 0, 100, 350, 1000 or 2000 ppm Pb acetate. Pups were sacrificed for homogenate receptor binding assays at 7, 14, 21 or 60 days of age. Postnatal Pb exposure generally facilitated DA receptor number (Bmax) development over the first 21 days of age, in both striatum and nucleus accumbens, without any apparent effects on receptor affinity (Kd values). Residual changes in Bmax were found for both D1 and D2 receptors at 60 days of age, with Bmax changes occurring in opposite directions in the two brain regions. D1 Bmax values were increased in striatum, and decreased in nucleus accumbens at PbB (blood lead levels) of > 50 ug/dl, whereas, at PbBs of 10-20 ug/dl, but not higher, D2 Bmax values were decreased in striatum but increased in nucleus accumbens. These findings suggest a preferential vulnerability of D2 receptors to lower Pb exposure concentrations and underscore the importance of Pb exposure level and brain region to resulting receptor changes. A linear relationship was observed between changes in nucleus accumbens D2 receptor Bmax values and Pb-induced changes in D2 sensitivity as derived from a drug discrimination study using littermates of offspring from the current study (Cory-Slechta et al., 1992), suggesting nucleus accumbens as a preferential site of Pb-induced D2-mediated effects.

Age Distribution↗

PubMed1993

Pulmonary changes induced by combined mouse beta-interferon (rMuIFN-beta) and irradiation in normal mice--toxic versus protective effects.

This study in normal mice was undertaken to investigate possible enhancement of pulmonary toxicity by interferon-beta (IFN-beta) combined with single doses of irradiation. A pharmacokinetic study preceded the toxicity study to determine the optimal route and timing of IFN administration. Graded single doses of radiation were combined with graded doses of IFN. Pulmonary toxicity was determined using endpoints of alveolar surfactant and procollagen in lung lavage fluid at 7 days, breathing frequency, lethality and histology. Increased lethality was seen when IFN was combined with irradiation at 12.5 Gy vs. irradiation alone. This occurred between 20 and 30 weeks post treatment with no increased breathing frequency or surfactant release, suggesting independent mechanisms of injury. Increased breathing frequency after 40 weeks, usually associated with fibrosis, was less pronounced for IFN treated vs. irradiation only controls. Ultrastructural studies at 72 weeks suggest reduced fibrosis in lungs of IFN treated vs. irradiation only controls. Supporting this was the finding that Procollagen III, a biosynthetic precursor of collagen, was increased in the lavage fluid at 7 days for all radiation doses but decreased with the addition of IFN at 12.5 and 15 Gy. Interferons can act either as sensitizers or radioprotectors, depending on the biological system and type of interferon. Our study suggests that while IFN-beta may increase the acute effects of radiation in the mouse lung, some protection from radiation-induced fibrosis, possibly related to alteration of immune mechanisms, may exist.

Animals↗

PubMed1992

Increased fibronectin mRNA in alveolar macrophages following in vivo hyperoxia.

Oxygen-mediated lung injury can stimulate a fibroproliferative response resulting in the alteration of the pulmonary extracellular matrix and subsequent scarring of parenchymal tissue. Fibronectin (FN), a component of the extracellular matrix, appears in increased quantities in fibrotic lung disease. Alveolar macrophages (AMs) are a potential source of this molecule. Using quantitative in situ hybridization, we demonstrated that AMs from rabbits acutely exposed to 100% oxygen (hyperoxia) for up to 64 h have 20-fold greater levels of FN mRNA relative to cells from control animals. When animals were allowed to recover in room air for up to 72 h after maximal oxygen exposure, AM FN mRNA abundance approached baseline levels. Furthermore, in oxygen-exposed animals, the fraction of lavaged cells expressing FN mRNA was increased 10-fold relative to controls. Although there was marked cell-to-cell variation, we conclude that the AM is a potential source of FN in the events leading to hyperoxia-induced pulmonary fibrosis.

Animals↗

PubMed1992

Cellular and molecular responses to lung injury in relation to induction of tissue repair and fibrosis.

Those factors that determine whether tissue injury is followed by regeneration and repair or irreversible destruction and fibrosis are only now being elucidated. This article examines the lung's response to injury, the prominent role of polypeptide growth factors and cytokines in directing tissue responses, and the effects of injury on cell-specific expression of a number of genes.

Bronchopulmonary Dysplasia↗

PubMed1991

Temporal sequence of early alterations in rat lung following thoracic X-irradiation.

The temporal patterns of several responses in the lungs of groups of rats administered two different thoracic doses of X-rays (7.5 and 15 Gy) were examined during a time frame within which radiation pneumonitis develops (1-13-week period) in order to assess for potential interrelationships among the responses. Endpoints surveyed included lung gravimetric and volumetric changes, changes in lavaged alveolar macrophage (AM) numbers, interstitial accumulations of mast cells (MC), and alterations in the amounts of lavaged phospholipids (PL), protein (P), and histamine (H). Sham-irradiated rats served as controls. Early (1 week), dose-dependent increases in lavageable PL were not accompanied by increases in lung weights or lavageable P. Elevations in lavaged PL continued for at least 5 weeks after exposure. By this time, lung weights, AM numbers, MC, and lavageable P, but not lavageable H, were all substantially increased in lungs that received the 15 Gy dose, whereas these changes were not observed at the lower dose. At later times (weeks 7 and 9), the hyperpermeability response following the 15 Gy exposure became less pronounced and the PL response also subsided, while lung MC continued to further increase and lavageable H became abnormally elevated. Maximal increases in the lung's permeability status after the 15 Gy exposure was coincidental with maximal increases in AM. An association of increases in AM and lung hyperpermeability, however, was not evident as of week 13 after the 7.5 Gy dose when lung weights and lavageable P were significantly elevated. For the X-ray doses examined, our results suggest that: (1) the early PL response to X-rays is independent of, and precedes, permeability changes in the lung; (2) the time to onset of an X-irradiation-induced increase in lung permeability is dose-dependent; (3) the progressive accumulation of MC in the lung following X-irradiation is dose-dependent; (4) excessive accumulations of interstitial MC after X-irradiation do not necessarily result in an increase in free H; and (5) free H in the lung does not appear to play a prominent role in the hyperpermeable response. Additionally, in conjunction with the findings of other investigators, our study suggests that the MC response to X-rays may be a fundamental component of the fibrogenic response.

Animals↗

PubMed1991

Mechanisms of nitrogen dioxide toxicity in humans.

These studies were undertaken to evaluate short-term respiratory effects and identify markers of nitrogen dioxide toxicity during exposures designed to approximate realistic conditions. With the development of bronchoalveolar lavage as a clinical investigative technique, the evaluation focused on the assessment of effects induced at the alveolar level. The exposure protocols were designed to assess the duration of nitrogen dioxide-induced effects and determine exposure-response relationships. Groups of normal, nonsmoking volunteers of both sexes between the ages of 18 and 40 years, without airway hyperreactivity, constituted the study population. The exposure protocols required a total of three to five days for each subject, depending on the timing of bronchoalveolar lavage. Subjects were exposed to nitrogen dioxide or air for three hours in a double-blind, randomized fashion in a 45-m3 environmental chamber, with intermittent exercise sufficient to quadruple minute ventilation. Pulmonary function was measured during and after exposure, and airway reactivity to carbachol was assessed before and after exposure. Lavaged cells were examined for their capacity to inactivate influenza virus and secrete IL-1 in vitro. Cell-free lavage fluid was analyzed for total protein, albumin, alpha 2-macroglobulin, arylsulfatase, and alpha 1-protease inhibitor. The studies were undertaken in three phases, each of approximately one year's duration. In Phase 1, 15 subjects were exposed to a background concentration of 0.05 parts per million2 (ppm) nitrogen dioxide and to three 15-minute peaks of 2.0 ppm, and underwent bronchoalveolar lavage 3.5 hours after nitrogen dioxide exposure. During Phase 2, 8 subjects were exposed to continuous 0.60 ppm nitrogen dioxide and underwent bronchoalveolar lavage 18 hours later. Finally, in Phase 3, 15 subjects were exposed to continuous 1.5 ppm nitrogen dioxide and underwent bronchoalveolar lavage 3.5 hours after exposure. No significant symptomatic or pulmonary function changes could be detected in response to any of the nitrogen dioxide exposures. However, a small but significant increase in airway reactivity was observed in normal subjects after exposure to 1.5 ppm nitrogen dioxide. Following the highest dose of carbachol (10 mg/mL), the forced expiratory volume in one second decreased 7.5 +/- 1.1 percent after nitrogen dioxide exposure compared to 4.8 +/- 1.1 percent after exposure to air (p less than 0.05). No symptoms were induced in any of the groups by the carbachol exposures. Analyses of cells recovered by bronchoalveolar lavage during all three phases revealed no differences in total cell recovery, cell viability, or differential cell counts.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1990

The production of alveolar macrophage-derived growth-regulating proteins in response to lung injury.

Tissue injury elicits an inflammatory response, one element of which is the activation of the local macrophage population. Macrophages are recognized as the source of multiple growth-regulating proteins, and are thus thought to play an important role in wound healing. Injury to the lung by exposure to oxidant gases, particulates, chemicals or drugs is often followed by replication of the cells of the alveoli. The growth-regulating proteins released by alveolar macrophages (AM) may be one mechanism which controls the proliferation of these cells. This article describes the AM growth factors, the cell types which they affect, and the injuries known to cause their release. In view of the multiplicity and overlapping functions of the macrophage growth factors, potential mechanisms which might regulate the growth response of the surrounding cells are also considered.

Growth Substances↗

PubMed1990

Changes in gene expression in hyperoxia-induced neonatal lung injury.

Exposure to high concentrations of oxygen (hyperoxia) can result in lung injury. The biochemical basis of this injury is poorly understood, but it is likely to include alterations in gene expression. Hyperoxia-induced (H-I) cDNAs have been molecularly cloned (Horowitz et al. J. Biol. Chem. 264: 7092-7095, 1989) from the lungs of an adult rabbit exposed to toxic levels of oxygen. One of them (H-I 1) was identified as encoding the tissue inhibitor of metalloproteinases (TIMP), a key regulatory protein of extracellular matrix turnover. Here we identify another clone (H-I 3) as encoding pulmonary surfactant apoprotein A (SP-A). We also show that in neonatal rabbits exposed to 100% oxygen for 96 h, the mRNAs corresponding to TIMP, SP-A, and another H-I gene are increased. These studies have begun to explore specific changes in gene expression associated with neonatal hyperoxic lung injury.

Animals↗

PubMed1989

Isolation of alveolar epithelial cells from lung tissue obtained at autopsy.

Lung alveolar epithelial cells have been studied in a variety of laboratory animal models, and studies of human alveolar epithelial cells are important for comparison to information obtained from animal studies. Autopsy material is a source of human cells for study. Studies of human autopsy material revealed variables that negatively affected the yield of viable cells. For specimens from adults, these included death greater than 12 h before cell isolation, obvious severe lung fibrosis, longstanding metabolic disorders, and lung congestion indicated by weight of the right middle lobe greater than 150 g. Samples from children yielded significant numbers of viable cells up to 18 h after death. For 17 specimens that conformed to the above criteria, approximately 8.5 x 10(6) alveolar cells were obtained per gram of tissue (tissue weights ranged from 30 to 108 g) using a procedure involving instillation of proteases into the airways. The cells could be further fractionated, and 10 to 15% of the mixed cells obtained were type II pneumocytes. Analysis of NADPH cytochrome-c-reductase distribution in subcellular fractions provided evidence that the cells obtained were intact. Phospholipid enzyme activities and synthetic activity were within the ranges previously found in laboratory studies of freshly obtained animal lungs. These results suggest that significant numbers of viable and functional human lung cells, including type II pneumocytes, can be obtained from autopsy material.

Animals↗

PubMed1989

Serum markers for prediction of pulmonary radiation syndromes. Part I: Surfactant apoprotein.

Detection of a biochemical marker indicating radiation lung injury prior to the onset of clinical pathologic events could prove valuable in patient management. An increased level of alveolar surfactant is one of the earliest detectable changes following lung irradiation, starting within hours of irradiation and persisting a maximum of 2-6 weeks. However, because broncho-alveolar lavage is impracticable and endothelial cell damage due to radiation results in changes in permeability of vessel wall with leakage of alveolar proteins into serum, identification of serum markers was sought. A series of experiments in rabbits are described that clearly demonstrate serum surfactant apoprotein is an accurate marker and predictor for later lethal radiation pneumonitis. At 3-7 days after graded single doses to lung, surfactant was found in the serum paralleling the dose response for lethality. Control studies with a physiologic agent such as terbutaline release alveolar surfactant, but no serum surfactant was detected. Monitoring serum surfactant could direct preventive intervention prior to clinicopathologic manifestation of pulmonary radiation syndromes.

Animals↗

PubMed1989

Nitrogen dioxide exposure in vivo and human alveolar macrophage inactivation of influenza virus in vitro.

Epidemiologic studies have reported an increased incidence of respiratory infections and illness in association with elevated indoor levels of nitrogen dioxide (NO2). Animal exposure studies have found that brief exposures to peak levels of NO2 produce greater morbidity than continuous lower level exposure. In order to examine the effect of NO2 inhalation on human alveolar macrophages, normal volunteers were exposed sequentially to air or NO2, by double-blind randomization, in an environmental chamber. Two exposure protocols with comparable concentration x time products were used: (a) continuous 0.60 ppm NO2 (n = 9), and (b) background 0.05 ppm NO2 with three 15-min peaks of 2.0 ppm (n = 15). Inhalation of NO2 caused no significant changes in pulmonary function or airway reactivity in either exposure protocol. Alveolar macrophages obtained by bronchoalveolar lavage 3 1/2 hr after exposure to continuous 0.60 ppm NO2 tended to inactivate influenza virus in vitro less effectively than cells collected after air exposure (1.96 vs 1.25 log10 plaque-forming units on Day 2 of incubation, P less than 0.07). Four of nine subjects accounted for the observed impairment in virus inactivation; cells from these four subjects demonstrated an increase in interleukin-1 (IL-1) production after NO2 vs air, whereas the five remaining subjects decreased IL-1 production after NO2. In contrast, intermittent peak exposure did not alter the rate of viral inactivation or IL-1 production. This methodology has the potential to identify pollutant effects on mechanisms of respiratory defense in humans.

Adult↗