Reports show that particulate matter (PM) is related to respiratory and cardiovascular diseases. We previously reported the biological effects of PM in vivo and the endocytosis of PM by primary neutrophils from mice. Cell lines can be used to elucidate the mechanism underlying immune responses in detail; however, information is limited regarding the functions of neutrophils after PM exposure. Here, we investigated the immune response of primary neutrophils and dimethyl sulfoxide (DMSO)- and all-trans retinoic acid (ATRA)-differentiated HL-60 (neutrophil-like) cells to PM. We showed that endocytosis by ATRA-HL cells was enhanced compared to that by DMSO-HL cells and that endocytosis in both cells was inhibited by dynamin inhibitors. A MEK inhibitor, but not p38 or JNK inhibitors, inhibited endocytosis. The MEK inhibitor also inhibited the differentiation of ATRA-HL cells to neutrophils. We identified that endocytosis of PM by neutrophils activated the MAPK ERK and p38 pathways. DMSO-HL and ATRA-HL cells both produced TNF-? and IL-8 after lipopolysaccharide (LPS) or PM treatment, whereas non-differentiated HL-60 cells did not. MCP-1 production was enhanced in DMSO-HL cells after LPS or PM treatment, whereas it was high in ATRA-HL cells. Reactive oxygen species (ROS) production was enhanced after PM treatment to DMSO-HL cells. Further, extracellular extracts promoted endocytosis. The MEK inhibitor also reduced the production of TNF-?, IL-8, and MCP-1. Taken together, ERK activation is key for both differentiation and endocytosis, and DMSO-HL cells at day 6 can serve as a model of inflammatory neutrophils, such as bronchus neutrophils, and a good tool to analyze the molecular events involved in immune responses to PM.
Authors: Wang D, Sennari Y, Shen M, Morita K, Kanazawa T, Yoshida Y
; Full Source: International Immunopharmacology. 2020 Apr 29;84:106510. doi: 10.1016/j.intimp.2020.106510. [Epub ahead of print]