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The efficacy of an "allergen-gene immunization" protocol in altering allergic response was examined. Intramuscular injection of rats with a plasmid DNA encoding a house dust mite allergen into the muscle results in its long-term expression and the induction of specific immune responses. Significantly, this approach prevents the induction of immunoglobulin E synthesis, histamine release in bronchoalveolar fluids, and airway hyperresponsiveness in rats challenged with aerosolized allergen. Furthermore, this suppression is persistent and can be transferred into naive rats by CD8+ T cells from gene-immunized rats. These findings suggest that allergen-gene immunization is effective in modulating allergic responses, and may provide a novel therapeutic approach for allergic diseases.

. Fullerene derivatives protect against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs. Am J Physiol Regul Integr Comp Physiol 287: R21-R26, 2004; 10.1152/ajpregu.00310. 2003.-Fullerene derivatives have often been used as effective scavengers for reactive oxygen species (ROS). This study was designed to test whether polyhydroxylated fullerene derivatives [C60(OH)7Ϯ2] protect against oxidative stress in cultured RAW 264.7 cells and ischemia-reperfused (IR) lungs. In RAW 264.7 cells, sodium nitroprusside (SNP, 1 mM) and H 2O2 (400 M) caused a marked (90%) decrease in cell viability, and this decrease was dose dependently reversed by pretreatment with C 60(OH)7Ϯ2 (10-50 M). The increase in ROS production induced by SNP and H 2O2 was significantly suppressed by C 60(OH)7Ϯ2. Also, the decrease in mitochondrial membrane potential induced by SNP and H 2O2 was significantly reversed by C 60(OH)7Ϯ2. However, high concentration of C 60(OH)7Ϯ2 (1 and 1.5 mM) lead to cell death (apoptosis or necrosis). In the isolated rat lung, the increases in pulmonary artery pressure and capillary filtration pressure induced by SNP during IR were reversed significantly by C 60(OH)7Ϯ2 (10 mg/kg). These results indicate that polyhydroxylated fullerene derivatives C 60(OH)7Ϯ2 at low concentrations protect against oxidative stress in RAW 264.7 cells and IR lungs.antioxidants; nitric oxide; reactive oxygen species LUNG TRANSPLANTATION has become an accepted and effective treatment for a variety of end-stage pulmonary diseases (10). Despite optimal lung preservation techniques, the lung remains extremely vulnerable to ischemia-reperfusion (IR) injury (6). IR injury occurs in the context of lung transplantation when blood supply is reintroduced to the ischemic graft at the completion of the implantation procedure (26). The alveolar oxygen represents a cofactor for the generation of reactive oxygen species (ROS), and continuous oxygen supply might thus enhance IR injury (21). IR lung injury plays a significant role in clinical situations, including lung transplantation as well as pulmonary thromboendarterectomy, reexpansion of collapsed lungs, and fibrinolysis after lung embolism (21). The pathophysiology of IR injury in the lung involves alveolarcapillary barrier leakage, neutrophil migration, interstitial and alveolar edema, tissue inflammation, and cell injury and death, alteration of nitric oxide synthase (NOS) activity, ROS production, lipid peroxidation, and proinflammation cytokine release (tumor necrosis factor-␣, interferon-␥, and interleukin-1) (26).Recently, many studies pointed out that IR injury could be attenuated by antioxidant therapy. In 1985, a novel allotrope was reported in which 60 carbon atoms (C 60 ) were arranged as a truncated icosahedron, with 60 vertices and 32 faces, 12 of which were pentagonal and 20 hexagonal (2, 12). Fullerene is a condensed aromatic ring with extended systems (11). Because the inventors commemorated the builder of American Rice University, Buckminister Fuller, C 60 was termed B...

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. Airway resistance due to alveolar gas compression measured by barometric plethysmography in mice. J Appl Physiol 98: 2204 -2218, 2005. First published January 27, 2005 doi:10.1152/japplphysiol.00869.2004.-We developed a method for measuring airway resistance (R aw) in mice that does not require a measurement of airway flow. An analysis of R aw induced by alveolar gas compression showed the following relationship for an animal breathing spontaneously in a closed box: R aw ϭ A btVb/[Vt (Ve ϩ 0.5Vt)]. Here Abt is the area under the box pressuretime curve during inspiration or expiration, V b is box volume, Vt is tidal volume, and V e is functional residual capacity (FRC). In anesthetized and conscious unrestrained mice, from experiments with both room temperature box air and body temperature humidified box air, the contributions of gas compression to the box pressure amplitude were 15 and 31% of those due to the temperature-humidity difference between box and alveolar gas. We corrected the measured Abt and Vt for temperature-humidity and gas compression effects, respectively, using a sinusoidal analysis. In anesthetized mice, Raw averaged 4.3 cmH 2O ⅐ ml Ϫ1 ⅐ s, fourfold greater than pulmonary resistance measured by conventional methods. In conscious mice with an assumed FRC equal to that measured in the anesthetized mice, the corrected R aw at room temperature averaged 1.9 cmH 2O ⅐ ml Ϫ1 ⅐ s. In both conscious mice and anesthetized mice, exposure to aerosolized methacholine with room temperature box air significantly increased R aw by around eightfold. Here we assumed that in the conscious mice both V t and FRC remained constant. In both conscious and anesthetized mice, body temperature humidified box air reduced the methacholine-induced increase in Raw observed at room temperature. The method using the increase in A bt with bronchoconstriction provides a conservative estimate for the increase in Raw in conscious mice. bronchoconstriction; methacholine; tidal volume; gas conditioning; conscious mice; anesthetized mice AIRWAY RESISTANCE (R aw ) in small animals is used to evaluate the efficacy of pharmacological agents in the treatment of allergic airway disease. In particular, the use of barometric plethysmography with conscious unrestrained mice in a closed box is particularly appealing because of its noninvasiveness and technical simplicity. Drorbaugh and Fenn (7) showed that tidal volume (V t ) is related to excursions in box pressure caused by changes in temperature and humidity of the airflow from the box to the alveolar space. This method for measuring V t has been validated in studies of newborn infants (7), monkeys (12), and mice (22); however, its accuracy has been questioned (9). The measurement of airway responsiveness from the cyclic variations of box pressure (17, 19) has been criticized because of the compounding effects of alveolar gas compression and the effects of temperature and humidity (gas conditioning). Lundblad et al. (17) from experiments in anesthetized mice concluded that the contribu...