Stimulation of human and rat alveolar macrophages by urban air particulates: effects on oxidant radical generation and cytokine production

Abstract

A number of epidemiological studies have associated increased cardiopulmonary mortality and hospital admissions with episodes of high particulate air pollution. Inhaled particles, with a mass median aerodynamic diameter <10 microm (PM10) reach the lower respiratory tract where they are phagocytized by alveolar macrophages (AM). Depending on particle composition, exposed AM may produce reactive oxygen species and inflammatory mediators resulting in vascular permeability changes, airway constriction, tissue injury, and inflammation. In the present study human and rat AM were reacted with a range of environmental particles, including oil fly ash (OFA), diesel dust (DD), and ambient air particles (UAP) collected in four urban centers. AM were tested for a chemiluminescence response induced by the particles as well as IL-6 and TNF production. While OFA in a dose range of 1000-10 microg/2-3 x 10(5) AM caused acute cytotoxicity above 100 microg in both human and rat AM (LDH release at 2 hr), DD and UAP were found to be nontoxic in the same dose range. However, after 20 hr of coincubation, UAP concentrations >167 microg/ml were also cytotoxic. Subcytotoxic concentrations of OFA induced a strong immediate chemiluminescence response by AM. A small but significant chemiluminescence response was induced by two out of three UAP tested, while no chemiluminescence was generated in response to DD. The magnitude of particle-induced chemiluminescence was not predictive of a cytokine response by either human or rat AM. TNF and IL-6 production was strongly induced by UAP over a range of noncytotoxic concentrations of particles. OFA induced only small amounts of TNF in a subset of human AM preparations, but not in rat AM. The AM cytokine response to UAP was partly inhibitable by polymyxin B, but not by the iron chelator deferoxamine, indicating that endotoxins but not transitional iron were cytokine-inducing moieties in the tested UAP preparations.