Antisense oligonucleotide to cofilin enhances respiratory burst and phagocytosis in opsonized zymosan-stimulated mouse macrophage J774.1 cells.
Phagocytes play a central role in the host defense system, and the relationship between the mechanism of their activation and cytoskeletal reorganization has been studied. We have previously reported a possible involvement of cofilin, an actin-binding protein, in phagocyte functions through its phosphorylation/dephosphorylation and translocation to the plasma membrane regions. In this work, we have obtained a new line of evidence showing an important role of cofilin in phagocyte functions using the mouse macrophage cell line J774.1 and an antisense oligonucleotide to cofilin. Upon stimulation with opsonized zymosan (OZ), cofilin was phosphorylated, and it accumulated around phagocytic vesicles. As the antisense oligonucleotide to cofilin, a 20-mer S-oligo corresponding to the sequence including the AUG translational initiation site was found to be effective. In the cells treated with the antisense oligonucleotide, the amount of cofilin was less than 30% of that in the control cells, and the level of F-actin was two or three times higher than that in the control cells before and throughout the cell activation. In the antisense oligonucleotide-treated cells, OZ-triggered superoxide production was three times faster than that in the control cells. Furthermore, phagocytosis of OZ was enhanced by the antisense. These results show that cofilin plays an essential role in the control of phagocyte function through regulation of actin filament dynamics.
Adachi
Reiko
R
National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Takeuchi
Kosei
K
Suzuki
Kazuhiro
K
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism*; D009895:Opsonin Proteins / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport / Q000502:physiology; D016897:Respiratory Burst / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D015054:Zymosan / Q000276:immunology / Q000378:metabolism*
D051339:Actin Depolymerizing Factors; D000199:Actins; D008840:Microfilament Proteins; D016376:Oligonucleotides, Antisense; D009895:Opsonin Proteins; D013481:Superoxides; D015054:Zymosan