TY - JOUR T1 - Organophosphorus pesticides increase inflammatory cytokines by activating macrophage Mac-1 JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/1393003.congress-2017.PA4926 VL - 50 IS - suppl 61 SP - PA4926 AU - Becky Proskocil AU - Pamela Lein AU - David Jacoby AU - Allison Fryer Y1 - 2017/09/01 UR - http://erj.ersjournals.com/content/50/suppl_61/PA4926.abstract N2 - Background: Organophosphorus pesticides (OPs) cause airway hyperreactivity in guinea pigs and are linked to development of asthma in humans. OPs increase inflammatory cytokine production by alveolar macrophages via unknown mechanisms. Mac-1 is an integrin expressed by macrophages that binds phosphorothionate moieties like those in OPs.Objective: We evaluated the role of macrophage Mac-1 in OP-induced increase in cytokines and growth factors and tested whether phosphorothionate OP metabolites similarly stimulate macrophages.Methods: In differentiated THP1 cells, a human monocyte cell line, Mac-1 was blocked with AbCD11b (Mac-1 blocking Ab) or heparin prior to treatment with the phosphorothionate OP chlorpyrifos (100 μM; 24 h) or lipopolysaccharide (LPS; 1 μg/ml). Other differentiated THP-1 cells were treated with OP metabolites diethyl phosphate, diethyl thiophosphate, or diethyl dithiophosphate. Tumor necrosis factor α, interleukin-1β, platelet-derived growth factor, and transforming growth factor-β RNA expression and secreted protein were measured.Results: OP-induced increase in cytokines and growth factors was prevented by blocking Mac-1 with either the Mac-1 blocking antibody or heparin. This effect was specific for Mac-1 since neither the blocking antibody nor heparin prevented LPS-induced increase in cytokine expression. Diethyl dithiophosphate also stimulated inflammatory cytokine expression and release.Conclusion: OPs promote inflammatory cytokine production in the airway through macrophage Mac-1 activation. Mac-1 is a promising therapeutic target for prevention of OP-related asthma.FUNDING: NIH: ES017592, HL124165, HL113023, AR061567. ER -