Two different mechanisms for modulation of bronchoconstriction in guinea-pigs by cyclooxygenase metabolites.

Leukotriene D(4) (LTD(4))-induced bronchoconstriction in guinea-pig airways has a cyclooxygenase (COX)-dependent component. The main objective of this study was to establish if prostaglandin (PG) D(2)-induced bronchoconstriction also was modulated by COX products. The effects of non-selective and selective COX-1 and COX-2 inhibitors on bronchoconstriction induced by LTD(4) and PGD(2) were investigated in the perfused and ventilated guinea-pig lung (IPL).

Effects of selective and non-selective COX inhibitors on antigen-induced release of prostanoid mediators and bronchoconstriction in the isolated perfused and ventilated guinea pig lung.

The contribution of cycloxygenase (COX)-1 and COX-2 in antigen-induced release of mediators and ensuing bronchoconstriction was investigated in the isolated perfused guinea pig lung (IPL). Antigen challenge with ovalbumin (OVA) of lungs from actively sensitised animals induced release of thromboxane (TX)A(2), prostaglandin (PG)D(2), PGF(2)(alpha), PGI(2) and PGE(2), measured in the lung effluent as immunoreactive TXB(2), PGD(2)-MOX, PGF(2)(alpha), 6-keto PGF(1)(alpha) and PGE(2), respectively. This release was abolished by the non-selective COX inhibitor flurbiprofen (10 microM).

Aggregates of ultrafine particles impair phagocytosis of microorganisms by human alveolar macrophages.

We investigated whether exposure of alveolar macrophages to aggregates of ultrafine carbon particles affected subsequent phagocytosis of microorganisms. Human alveolar macrophages were obtained by bronchoalveolar lavage and exposed to aggregates of ultrafine carbon particles or diesel exhaust particles (DEP) for 20 h before measurements of phagocytosis. The particle loads were estimated to be comparable to those of air pollution exposure with established health effects in humans.

A novel method to aerosolize powder for short inhalation exposures at high concentrations: isolated rat lungs exposed to respirable diesel soot.

More efficient methods are needed to aerosolize dry powders for short-duration inhalation exposures at high concentrations. There is an increasing need to reach the peripheral lung with dry powder medications as well as with collected ambient aerosol particulates in environmental research projects. In a novel aerosol generator, a fixed volume of compressed air was used to create a short burst of a highly concentrated aerosol in a 300-ml holding chamber.

Interactions among three classes of mediators explain antigen-induced bronchoconstriction in the isolated perfused and ventilated guinea pig lung.

Intravascular challenge of isolated perfused and ventilated guinea pig lung (IPL) from actively sensitized guinea pigs, with cumulatively increasing (10-10,000 microg) doses of ovalbumin (OVA), resulted in dose-dependent and reproducible reductions in lung conductance. The antihistamines mepyramine (1 microM) and metiamide (1 microM), the leukotriene antagonist zafirlukast (0.1 microM), or the cyclooxygenase enzyme (COX) inhibitor diclofenac (10 microM) each caused a parallel and rightward shift in the dose-response relation for OVA, providing evidence for contributions of histamine, cysteinyl-leukotrienes, and COX products to the OVA-induced bronchoconstriction in the IPL.

Effects of thermal degradation products from polyurethane foams based on toluene diisocyanate and diphenylmethane diisocyanate on isolated, perfused lung of guinea pig.

Objectives: The composition of thermal degradation products from two types of polyurethane foams, one based on toluene diisocyanate (TDI) and the other on diphenylmethane diisocyanate (MDI), was analyzed and their toxic lung effects were compared.

Methods: Isolated perfused lungs of guinea pig were subjected to thermal decomposition products of polyurethane foams from an aerosol generator with compartments for diluting, mixing, and sampling.

Results: Thermal degradation of MDI-based polyurethane foams released MDI, phenyl isocyanate, and methyl isocyanate.

Experimental and calculated parameters on particle phagocytosis by alveolar macrophages.

Phagocytosis of three types of fluorescein-labeled test particles by rat alveolar macrophages (AM) were studied: spherical silica (3.2 microm), heat-killed Candida albicans (3.8 microm), and heat-killed Cryptococcus neoformans (6.