Dimethyl 2,2-dichlorovinyl phosphate (DDVP) markedly decreases the expression of perforin, granzyme A and granulysin in human NK-92CI cell line.
Natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocyte (CTL) cells kill target cells by the directed release of cytolytic granules that contain perforin, granzymes and granulysin. We previously have found that dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide significantly inhibited NK, LAK and CTL activities via the inhibition of granzyme activity. To further explore the mechanism of organophosphorus pesticide-induced inhibition of cell-mediated cytolysis, we asked here whether organophosphorus pesticides affect the expression of perforin, granzyme and granulysin in NK cells. We used NK-92CI cell, an interleukin-2 (IL-2) independent human NK cell line. We confirmed that NK-92CI cells express CD56 surface marker, perforin, granzyme A and granulysin by flow cytometry and immunofluorescence microscope, and that it is highly cytotoxic to K562 cells in chromium release assay. We found that DDVP significantly decreases the expression of perforin, granzyme A and granulysin in NK-92CI cells in a dose-dependent manner. Immunocytochemical results showed that DDVP significantly decreases perforin, granzyme A and granulysin positive granules in NK-92CI cell, which may be due to the degranulation. We also found that DDVP have a modest, but a significant inhibitory effect on the transcription of mRNA of perforin, granzyme A and granulysin.
Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. qing-li@nms.ac.jp
Qing
Q
Li
Ari
A
Nakadai
Masamichi
M
Ishizaki
Kanehisa
K
Morimoto
Atsushi
A
Ueda
Alan M
AM
Krensky
Tomoyuki
T
Kawada
D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics; D019002:CD56 Antigen / Q000096:biosynthesis; D002470:Cell Survival / Q000187:drug effects; D004006:Dichlorvos / Q000633:toxicity*; D005434:Flow Cytometry; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry; D007306:Insecticides / Q000633:toxicity*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics
D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; C075005:GNLY protein, human; D007306:Insecticides; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin; D004006:Dichlorvos; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human