STIMULATION OF HUMAN AND RAT ALVEOLAR MACROPHAGES BY URBAN AIR PARTICULATES - EFFECTS ON OXIDANT RADICAL GENERATION AND CYTOKINE PRODUCTION

A number of epidemiological studies have associated increased cardiopu lmonary mortality and hospital admissions with episodes of high partic ulate air pollution. Inhaled particles, with a mass median aerodynamic diameter <10 mu m (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 inflam matory mediators resulting in vascular permeability changes, airway co nstriction, tissue injury, and inflammation. In the present study huma n and rat AM were reacted with a range of environmental particles, inc luding oil fly ash (OFA), diesel dust (DD), and ambient air particles (UAP) collected in four urban centers. AM were tested for a chemilumin escence response induced by the particles as well as IL-6 and TNF prod uction. While OFA in a dose range of 1000-10 mu g/2-3 x 10(5) AM cause d acute cytotoxicity above 100 mu g in both human and rat AM (LDH rele ase at 2 hr), DD and UAP were found to be nontoxic in the same dose ra nge. However, after 20 hr of coincubation, UAP concentrations >167 mu g/ml were also cytotoxic. Subcytotoxic concentrations of OFA induced a strong immediate chemiluminescence response by AM. A small but signif icant chemiluminescence response was induced by two out of three UAP t ested, 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 productio n was strongly induced by UAP over a range of noncytotoxic concentrati ons 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 chelat or deferoxamine, indicating that endotoxins but not transitional iron were cytokine-inducing moieties in the tested UAP preparations. (C) 19 96 Academic Press, Inc.