We have investigated the possibility that tumor necrosis factor alpha (TNF) plays a role in the increased airway permeability and an inflammatory response following an acute ozone (O3) exposure. Male Sprague-Dawley rats were injected, intraperitoneally, with either rabbit anti-mouse antibody to TNF (anti-TNF) or preimmune rabbit serum, 2 h before a 3-h exposure to O3 or purified air. Permeability, as determined by [99mTc] diethylenetriamine pentaacetate (DTPA) transport, total protein and albumin concentrations in the bronchoalveolar lavage (BAL), and the inflammatory cell response in the BAL were assessed 10 h after the exposure was completed. The O3-exposed group that was injected with anti-TNF showed a significant decrease in permeability to DTPA in comparison to the O3- exposed group injected with preimmune rabbit serum. There was no difference between the anti-TNF group and the purified air group. In contrast, the total protein and albumin levels in the BAL were significantly greater in both of the O3-exposed groups than in the purified air group. The concentrations of protein and albumin in the anti-TNF group did, however, show an attenuating trend when compared to the preimmune O3-exposed group. The polymorphonuclear leukocytes (PMNs) in BAL of the anti-TNF group also showed an attenuating trend when compared to the preimmune O3-exposed group, but both of these O3-exposed groups were significantly greater than the purified air group. Lung sections stained with naphthol AS-D chloroacetate esterase showed an increase in the number of stained PMNs in the anti-TNF group in comparison to the preimmune O3- and air-exposed groups. These data suggest that TNF plays a role in the increase in tracheal permeability as determined by DTPA transport, while the contributing role that TNF plays in bronchoalveolar permeability and the inflammatory response seen following an acute exposure to 0.8 ppm O3 is less evident.

This study involves the analysis of the sequence of changes in lung epithelial permeability, free cells in the airways, prostaglandin E2 (PC€;J levels, polymorphonuclear leukocyte (PMN) flux, and alveolar lesions in rats exposed to 0.8 ppm ozone (03 for 3 h and then studied at 4-h intervals up to 24 h postexposure. Protein content of the bronchoalveolar lavage (BAL) increased immediately after O3 exposure and returned to control levels by 16 h postexposure. Albumin concentration in the BAL also increased with time after 0, exposure, but the increase was more gradual than the protein increase. The lower albumin concentrations at 20 and 24 h postexposure were still higher than the control levels. While the total protein in the BAL could be attributed to tissue injury and increased transmucosal transport, the albumin primarily reflected elevated transport from the serum. Total cells in the BAL decreased immediately after the 0, exposure, but returned to near normal levels by 4 h. PGE, levels did not change significantly after 0, exposure. PMNs in the lung sections increased in number with time, peaked at 8 h, and returned to normal levels by 76 h following 0, exposure. The data suggest that the permeability changes may be produced by the direct toxic effects of 0, on the airway epithelia, but the PMNs contribute to the injury process, especially at the later stages. Lung lesions, represented by the thickening of the alveolar septae and increased cellularity, were present at 72 h postexposure and increased with time, thus coinciding with declining permeability at the later stages. The morphological changes lag behind the functional perturbations and appear to represent a phase of functional recovery

No abstract

The polypeptide β-endorphin binds to cultured bovine adrenal cortical cells in a naloxone insensitive manner, β-endorphin and N-Acetyl-β-endorphin are equipotent in inhibiting binding. The amino terminal 27 amino acid fragment referred to as β-endorphin[1-27] shows no ability to inhibit binding, whereas the carboxy-terminal tetrapeptide Lys-Lys-Gly-Glu partially inhibits binding. ACTH, angiotensin II and met-enkephalin show little or no ability to inhibit β-endorphin binding. Competition bin-ding reveals an apparently single affinity class with Kd of 33 nM. Molecular cross linking experiments reveal putative receptor subunits of 85 kD, 64 kD, 54 kD and 44 kD. The lower molecular weight bands are preferentially cross-linked by a hydrophobic cross linking reagent, in contrast to the two higher molecular weight bands, which are cross linked equally by hydrophobic and water soluble cross linking reagents. The β-endorphin binding characteristics of adrenal cortical cells revealed here are quite similar to those of a class of non-opioid β-endorphin receptors previously shown to exist in cells of the immune system.