Pannexin-1 influences peritoneal cavity cell population but is not involved in NLRP3 inflammasome activation

Abstract

Pannexin-1 (Panx1) forms nonselective large channel in cell plasma membrane and has been shown to be associated with NLRP3 inflammasome activation, ATP release and phagocytes recruitment. In the current study, by manipulation of Panx1 expression in human myeloid cells and application of Panx1 defi cient mice, we failed to fi nd a correlation between Panx1 and NLRP3 inflammasome activation, although an interaction between these two proteins was evident. However, in thioglycollate induced peritonitis, Panx1 defi cient mice showed much more phagocytes infiltration. Further analyses showed that mice defi cient for Panx1 exhibited enlarged F4/80^lowGr1^-Ly6C^-cell population in the peritonea. Our study thus reveals an important role for Panx1 in regulation of peritoneal cell population and peritonitis development.

Keywords

innate Immunity / inflammasome / NLRP3 / Pannexin-1 / peritonitis

References

[1] Agostini, L., Martinon, F., Burns, K., McDermott, M.F., Hawkins, P.N., and Tschopp, J. (2004). NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflamatory disorder. Immunity 20, 319-325.10.1016/S1074-7613(04)00046-9
[2] Bruzzone, R., Hormuzdi, S.G., Barbe, M.T., Herb, A., and Monyer, H. (2003). Pannexins, a family of gap junction proteins expressed in brain. Proc Natl Acad Sci U S A 100, 13644 -13649 .10.1073/pnas.2233464100
[3] Chekeni, F.B., Elliott, M.R., Sandilos, J.K., Walk, S.F., Kinchen, J.M., Lazarowski, E.R., Armstrong, A.J., Penuela, S., Laird, D.W., Salvesen, G.S., . (2010). Pannexin 1 channels mediate ′fi ndme′ signal release and membrane permeability during apoptosis. Nature 467, 863-867.10.1038/nature09413
[4] Geissmann, F., Jung, S., and Littman, D.R. (2003). Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19, 71-82 .10.1016/S1074-7613(03)00174-2
[5] Ghosn, E.E., Cassado, A.A., Govoni, G.R., Fukuhara, T., Yang, Y., Monack, D.M., Bortoluci, K.R., Almeida, S.R., and Herzenberg, L.A. (2010). Two physically, functionally, and developmentally distinct peritoneal macrophage subsets. Proc Natl Acad Sci U S A 107, 2568-2573 .10.1073/pnas.0915000107
[6] Gulbransen, B.D., Bashashati, M., Hirota, S.A., Gui, X., Roberts, J.A., MacDonald, J.A., Muruve, D.A., McKay, D.M., Beck, P.L., Mawe, G.M., . (2012). Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis. Nat Med 18, 600-604 .10.1038/nm.2679
[7] Hu, Y., Mao, K., Zeng, Y., Chen, S., Tao, Z., Yang, C., Sun, S., Wu, X., Meng, G., and Sun, B. (2010). Tripartite-motif protein 30 negatively regulates NLRP3 inflammasome activation by modulating reactive oxygen species production. J Immunol 185, 7699-7705 .10.4049/jimmunol.1001099
[8] Kanneganti, T.D., Lamkanfi, M., Kim, Y.G., Chen, G., Park, J.H., Franchi, L., Vandenabeele, P., and Nunez, G. (2007). Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling. Immunity 26, 433-443 .10.1016/j.immuni.2007.03.008
[9] Kienitz, M.C., Bender, K., Dermietzel, R., Pott, L., and Zoidl, G. (2011). Pannexin 1 constitutes the large conductance cation channel of cardiac myocytes. J Biol Chem 286, 290-298 .10.1074/jbc.M110.163477
[10] Locovei, S., Wang, J., and Dahl, G. (2006). Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium. FEBS Lett 580, 239-244 .10.1016/j.febslet.2005.12.004
[11] Panchin, Y., Kelmanson, I., Matz, M., Lukyanov, K., Usman, N., and Lukyanov, S. (2000). A ubiquitous family of putative gap junction molecules. Curr Biol 10, R473-474 .10.1016/S0960-9822(00)00576-5
[12] Pelegrin, P., and Surprenant, A. (2006). Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 25, 5071-5082 .10.1038/sj.emboj.7601378
[13] Pelegrin, P., and Surprenant, A. (2007). Pannexin-1 couples to maitotoxin-and nigericin-induced interleukin-1beta release through a dye uptake-independent pathway. J Biol Chem 282, 2386-2394 .10.1074/jbc.M610351200
[14] Qu, Y., Misaghi, S., Newton, K., Gilmour, L.L., Louie, S., Cupp, J.E., Dubyak, G.R., Hackos, D., and Dixit, V.M. (2011). Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J Immunol 186, 6553-6561 .10.4049/jimmunol.1100478
[15] Zhang, X., Goncalves, R., and Mosser, D.M. (2008). The isolation and characterization of murine macrophages. Curr Protoc Immunol Chapter 14, Unit 14 11.10.1002/0471142735.im1401s83