Inflammatory effects of inhaled endotoxin-contaminated metal working fluid aerosols in rats.

Exposure to aerosols generated from water-soluble metal-working fluids (MWF) is associated with numerous respiratory symptoms consistent with an acute pulmonary inflammatory event. Previous studies in mice and guinea pigs have implicated endotoxin contamination of MWF as the causative agent responsible for inducing pulmonary neutrophilia and decrements in airway conductance. However, little information is known about the relationship between endotoxin-contaminated MWF exposure and changes in airway physiology. The present study, utilizing a rat model, has demonstrated that exposure to 10 mg/m3 with endotoxin (0 to 3.2 micrograms/m3) resulted in a time- and concentration-dependent migration of neutrophils in the lung tissue's interstitial spaces as well as the lavageable airways. In contrast to other airborne toxicants, where neutrophil infiltration of the lung has been associated with hyperresponsive airways, the endotoxin-induced neutrophilia observed in the present study was not associated with airway hyperresponsiveness to challenge with the muscarinic agent methacholine or with permeability damage to the lung. Bronchoalveolar lavage (BAL)-recovered neutrophils demonstrated no adverse effects as a result of endotoxin-contaminated MWF exposure. In contrast, a population of alveolar macrophages was observed to be enlarged in size and demonstrated an increased sensitivity to oxidative metabolism when challenged with phorbol myristate acetate, consistent with being at a relatively high state of activation. These results suggest that while endotoxin contamination of MWF is capable of producing an acute inflammatory event, other predisposition factors may be required to induce alterations in pulmonary physiology.

Hyperresponsive airways correlate with lung tissue inflammatory cell changes in ozone-exposed rats.

The role of inflammatory cell infiltration in the development of hyperresponsiveness of the airways to muscarinic challenge remains poorly understood. Unlike previous investigations that only examined conducting airway inflammation, the present study utilized both bronchoalveolar lavage (BAL) and lung tissue digestion to determine rat lung inflammatory cell contents following a 4-h exposure to 2 ppm ozone. Immediately following ozone exposure, neutrophil content of the lung tissue was significantly increased and reached a value that was fourfold higher than air-exposed controls by 3 h postexposure. Although lavage-recovered neutrophils were elevated at 24 h, tissue neutrophil numbers had returned to control values. This transient elevation of tissue neutrophils directly correlated with an elevation and subsequent decline of airway hyperresponsiveness, measured as a decrease in the intravenous dose of methacholine provoking a 200% increase in airway resistance (PD(200)R). Animals rendered neutropenic with a rabbit anti-rat neutrophil serum prior to exposure were protected from ozone-induced hyperresponsive airways, further demonstrating an association between neutrophil infiltration into the lung and altered airway physiology. Although BAL-recovered neutrophils demonstrated no adverse effects as a result of ozone exposure, macrophages were not only found to be necrotic but also displayed altered oxidative metabolism when challenged with phorbol myristate acetate. Thus, changes in the microenvironment of the airways smooth muscle were shown to be associated with transient accumulation of neutrophils within the lung tissue and abnormalities of bronchoalveolar lavage-recovered macrophages.