Role of the alveolar macrophage in lung injury: studies with ultrafine particles

Abstract

We conducted a series ofexperiments with ultrfine particles (-20 nm) and larger particles (< 200 nm) of "nuisance" dusts to evaluate the involvement of alveolar macrophages (AM) in particle-induced lung injury and particle transloca- tion in rats. After intratracheal instillation of both ultrafine particles and larger particles ofTO2, we found a highly in- creased interstitial access of the ultrafine particles combined with a large acute infmmatory reaction as determined by lung lavage parameters. An additional experiment revealed that intratracheal nstillation of ph ctized ultrfine 1102 particles (inside AM) prvented both the puhonary inflam ry reaction and the interl access ofthe utrafin particles. Another experiment showed that the influx of polymorphonuclear cells (PMN) into the alveolar space unexpectedly decreased with higher doses ofultrafine particles, wheras alveolar epithelial permeability (protein leakage) increased. The divergence between PMN influx into the alveolar space and changes in alveolar epithelal permeability implies that they are separate events. Pulmonary inflammatory parameters determined by lung lavage analysis correlated best with the surface area ofthe retained particles rather than with their mass, volume, or numbers. Because higher doses resulted in an increased interstitialized fraction of particles, we suggest that inflamatory events induced by particles in the in- terstitial space can modify the inflammation in the alveolar space detectable by lung lavage. Our results demonstrate the dual role of AM for modifying particle-induced lung injury, i.e., both preventing such injury and contributing to it. We-& conclude that the increased pulmonary toxicity ofultrafine particles is related to their larger surface areaand to their in- creased interstitial access. Further, we suggest that the inte stizaon ofparticles isimportant for inducion ofpulmonary fibrotic reactions and that ultrafine particles of nuisance dusts should have different threshold limit values for occupa- tional exposure because of their increased puhnonary toxicity.