Phagocytosis of particulate air pollutants by human alveolar macrophages stimulates the bone marrow

Epidemiologic studies have shown an association between the level of ambient particulate matter, 10 mm (PM10) and cardiopulmonary mortality. We have shown that exposure of rabbits to PM10 stimulates the bone marrow. In this study, we determined whether human alveolar macrophages (AMs) that phagocytose atmospheric PM10 produce mediators capable of stimulating the bone marrow. AMs incubated with PM10 for 24 h produced tumor necrosis factor-alpha in a dose-dependent manner (86.8 +/- 53.29 pg/ml with medium alone; 1,087.2 +/- 257.3 pg/ml with 0.1 mg/ml of PM10; P < 0.02). Instillation of the supernatants from AMs incubated with 0.1 mg/ml of PM10 into the lungs of rabbits (n = 6) increased circulating polymorphonuclear leukocyte (PMN) and band cell counts as well as shortened the PMN transit time through the bone marrow (87.9 +/- 3.3 h) compared with unstimulated human AMs (104.9 +/- 2.4 h; P < 0.01; n = 5 rabbits). The supernatants from rabbit AMs incubated with 0.1 mg/ml of PM10 (n = 4 rabbits) caused a similar shortening in the PMN transit time through the bone marrow (91.5 +/- 1.6 h) compared with human AMs. We conclude that mediators released from AMs after phagocytosis of PM10 induce a systemic inflammatory response that includes stimulation of the bone marrow.