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.
DeLorme
Michael P
MP
Department of Occupational and Environmental Health Sciences, Wayne State University, Detroit, Michigan, USA. michael.p.delorme@usa.dupont.com
Gao
Xiufeng
X
Doyon-Reale
Nicole
N
Barraclough-Mitchell
Holly
H
Bassett
David J P
DJ
D000280:Administration, Inhalation; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004731:Endotoxins / Q000633:toxicity*; D005434:Flow Cytometry; D007219:Industrial Oils / Q000633:toxicity*; D007249:Inflammation; D008297:Male; D008669:Metallurgy; D016210:Methacholine Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012120:Respiration Disorders / Q000139:chemically induced*; D012129:Respiratory Function Tests; D012137:Respiratory System / Q000187:drug effects*; D018709:Statistics, Nonparametric
D000336:Aerosols; D004731:Endotoxins; D016210:Methacholine Chloride