Susceptibility to ozone-induced airway inflammation is associated with decreased levels of surfactant protein D

BACKGROUND: Ozone (O(3)), a common air pollutant, induces exacerbation of asthma and chronic obstructive pulmonary disease. Pulmonary surfactant protein (SP)-D modulates immune and inflammatory responses in the lung. We have shown previously that SP-D plays a protective role in a mouse model of allergic airway inflammation. Here we studied the role and regulation of SP-D in O(3)-induced inflammatory changes in the lung. METHODS: To evaluate the effects of O(3 )exposure in mouse strains with genetically different expression levels of SP-D we exposed Balb/c, C57BL/6 and SP-D knockout mice to O(3 )or air. BAL cellular and cytokine content and SP-D levels were evaluated and compared between the different strains. The kinetics of SP-D production and inflammatory parameters were studied at 0, 2, 6, 12, 24, 48, and 72 hrs after O(3 )exposure. The effect of IL-6, an O(3)-inducible cytokine, on the expression of SP-D was investigated in vitro using a primary alveolar type II cell culture. RESULTS: Ozone-exposed Balb/c mice demonstrated significantly enhanced acute inflammatory changes including recruitment of inflammatory cells and release of KC and IL-12p70 when compared with age- and sex-matched C57BL/6 mice. On the other hand, C57BL/6 mice had significantly higher levels of SP-D and released more IL-10 and IL-6. Increase in SP-D production coincided with the resolution of inflammatory changes. Mice deficient in SP-D had significantly higher numbers of inflammatory cells when compared to controls supporting the notion that SP-D has an anti-inflammatory function in our model of O(3 )exposure. IL-6, which was highly up-regulated in O(3 )exposed mice, was capable of inducing the expression of SP-D in vitro in a dose dependent manner. CONCLUSION: Our data suggest that IL-6 contributes to the up-regulation of SP-D after acute O(3 )exposure and elevation of SP-D in the lung is associated with the resolution of inflammation. Absence or low levels of SP-D predispose to enhanced inflammatory changes following acute oxidative stress

Elucidating the Mechanism of the Halide-Induced Ligand Rearrangement Reaction

The formation of heteroligated Rh^I complexes containing two different hemilabile phosphinoalkyl ligands, (κ²-Ph₂PCH₂CH₂S-Aryl)­(κ¹-Ph₂PCH₂CH₂O-C₆H₅)­RhCl, through a halide-induced ligand rearrangement (HILR) reaction has been studied mechanistically. The half-life of this rearrangement reaction depends heavily on the Rh^I precursor used and the chelating ability of the phosphinoalkyl thioether (PS) ligand, while the chelating ability of the phosphinoalkyl ether (PO) ligand has less of an effect. An intermediate complex which contains two PO ligands, (nbd)­(κ¹-Ph₂PCH₂CH₂O-C₆H₅)₂RhCl (nbd = norbornadiene), converts to (nbd)­(κ¹-Ph₂PCH₂CH₂O-C₆H₅)­RhCl resulting in a free PO ligand. The free PO ligand can then react with a homoligated PS complex [(κ²-Ph₂PCH₂CH₂S-Aryl)₂Rh]^<b>+</b>Cl^– producing the heteroligated product. The PS ligand generated during the reaction pathway can be trapped by the monoligated PO complex (nbd)­(κ¹-Ph₂PCH₂CH₂O-C₆H₅)­RhCl, leading to the formation of the same heteroligated product. In this study, some of the key intermediates and reaction steps underlying the HILR reaction have been identified by variable temperature ³¹P­{¹H} NMR spectroscopy and in two cases by single-crystal X-ray diffraction studies. Significantly, this work provides mechanistic insight into the HILR process, which is a key reaction used to prepare a large class of highly sophisticated three-dimensional metallosupramolecular architectures and allosteric catalysts