Insoluble components of concentrated air particles mediate alveolar macrophage responses in vitro

We sought to characterize the bioactive constituents of concentrated ambien t air particles (CAPs) through correlation of alveolar macrophage (AM) biol ogical responses (production of TNF, macrophage inflammatory protein (MIP-2 ), nitrite; cell viability) to components of particle samples. CAPs samples collected on different days showed a range of bioactivity and a strong cor relation was found between AM cytokine release and increased AM light scatt er, a how cytometric measure of relative particle load. Evaluation of solub le and insoluble fractions of CAPs suspensions indicate that 1) most biolog ical effects on AMs are mediated by insoluble components and certain partic le adsorbed factors such as endotoxin; 2) the variable bioactivity of CAPs collected on different days arises primarily from differences in the relati ve proportion of insoluble and soluble mass present in particle suspensions ; and 3) the activation state of the AM influences which insoluble componen ts are most bioactive. Use of endotoxin neutralizing agents (e.g., polymyxi n-B) showed particle-adsorbed endotoxin in CAPs suspensions causes activati on of normal (control) AMs while other (nonendotoxin) components are predom inantly responsible for the enhanced cytokine release observed by primed AM s incubated with CAPs. The AM biological response did not correlate with an y of a panel of elements quantified within insoluble CAPs samples (Al, Cd, Cr, Cu, Fe, Mg, Mn, Ni, S, Ti, V). These data demonstrate an important role for cell activation and phagocytosis of insoluble particulate matter in th e response of AMs to CAPs suspensions. (C) 2000 Academic Press.