Jill Poole1,2, Geoffrey M. Thiele1,3,4, Neil E. Alexis5, Angela Burrell1,2, Conrad Parks1,2, Debra J. Romberger1,2
1Omaha Veterans Administration Medical Center, Omaha
2Pulmonary, Critical Care, Sleep and Allergy Section and
3Rheumatology and Immunology Section
4Rheumatology and Immunology Section; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska; and
5University of North Carolina School of Medicine, Center for Environmental Medicine, Asthma and Lung Biology, Chapel Hill, North Carolina
Tóm tắt
Organic dust exposure in agricultural animal environments results in airway diseases. Dendritic cells (DCs) orchestrate inflammatory immune response in the airways, but little is known about how organic dust affects differentiation and maturation of monocyte-derived immature and mature DCs (iDCs, mDCs). Peripheral blood monocytes were differentiated in vitro into iDCs with granulocyte-macrophage colony stimulating factor + IL-4 (6 days) with and without swine facility organic dust extract (ODE, 0.1%). Unlike control iDCs, ODE-conditioned iDCs maintained key monocyte properties (increased mCD14, increased phagocytic ability) while expressing DC features [increased mCD83, HLA-DR, CD80, CD86, diminished cytokine (TNF-α, IL-6) responsiveness]. At day 6, iDCs were cultured for an additional 48 h ( days 7 and 8) with lipopolysaccharide (LPS) to induce mDCs. ODE-conditioned mDCs maintained high expression of mCD14+ and elevated phagocytosis while their DC features weakened as evidenced by decreased CD11c, CD83, HLA-DR, CD86, and CCR7 expression and reduced lymphocyte-stimulating capacity. Similar results were observed when monocytes were exposed to ODE for only the first 48 h and with ODE depleted of endotoxin. Control iDCs exposed to ODE during the final 2 days of iDC maturation ( days 7 and 8) did not differ from control (no ODE) iDCs in surface marker expression and phagocytic ability, but exhibited enhanced lymphocyte-stimulating capacity. Dust exposure alters monocyte differentiation to iDCs and prevents maturation of iDC to mDCs. The first 48 h of monocyte differentiation appears to be the susceptible period to exposure. Environmental exposures present during early monocyte differentiation may impact the critical balance of DCs in the lung.
