Perfluoroisobutylene-Induced Acute Lung Injury and Mortality are Heralded by Neutrophil Sequestration and Accumulation

Abstract

Perfluoroisobutylene-Induced Acute Lung Injury and Mortality are Heralded by Neutrophil Sequestration and Accumulation: Hemei WANG, et al. Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences—Perfluoroisobutylene (PFIB) is a highly toxic and potentially life—threatening pneumoedematogenic agent that is usually encountered in case of fire or industrial accidents. The mechanisms by which the toxicity of PFIB are mediated remain unclear. To investigate the role of neutrophil⁄ polymorphonuclear leukocytes (PMN) in the pathogenesis of PFIB-induced acute lung injury (ALI), mice and rats were exposed to a sublethal concentration of PFIB (130 mg/m3 and 140 mg/m3, respectively) for 5 min in a flow-past whole—body chamber. The general pattern for the time-course of the increase in lung PMN infiltration as measured by lung myeloperoxidase (MPO) assay was shown to be rather similar to that of the lung injury indexed by both the total protein increase in the bronchoalveolar lavage fluid (BALF) and lung wet—to—dry weight ratio, except for the earlier start and the maximal time-point of the increase in lung PMN infiltration. When neutropenia was obtained by cyclophosphamide pretreatment, death of the mice induced by an over—LCt50 dose of PFIB (at 190 mg⁄m3 for 5min) dropped dramatically, and this was very well supported by observations in the BALF total protein analysis, histopathological as well as ultrastructural studies. These results confirmed that PFIB inhalation—induced ALI and mortality are heralded by the influx of PMNs into the lung. (J Occup Health 2001; 43: 331-338)