Lipopolysaccharide induces CD38 expression and solubilization in J774 macrophage cells
- 274 Downloads
CD38, an ADP ribosyl cyclase, is a 45 kDa type II transmembrane protein having a short N-terminal cytoplasmic domain and a long C-terminal extracellular domain, expressed on the surface of various cells including macrophages, lymphocytes, and pancreatic β cells. It is known to be involved in cell adhesion, signal transduction and calcium signaling. In addition to its transmembrane form, CD38 is detectable in biological fluids in soluble forms. The mechanism by which CD38 is solubilized from the plasma membrane is not yet clarified. In this study, we found that lipopolysaccharide (LPS) induced CD38 upregulation and its extracellular release in J774 macrophage cells. Furthermore, it also increased CD38 expression at the mRNA level by activating the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway. However, LPS decreased the levels of CD38 in the plasma membrane by releasing CD38 into the culture supernatant. LPS-induced CD38 release was blocked by the metalloproteinase-9 inhibitor indicating that MMP-9 solubilizes CD38. In conclusion, the present findings demonstrate a potential mechanism by which C38 is solubilized from the plasma membrane.
KeywordsCD38 interferon β JAK-STAT lipopolysaccharide macrophages metalloproteinase-9
Unable to display preview. Download preview PDF.
- Dianzani, U., Funaro, A., DiFranco, D., Garbarino, G., Bragardo, M., Redoglia, V., Buonfiglio, D., De Monte, L.B., Pileri, A., and Malavasi, F. (1994). Interaction between endothelium and CD4+CD45 RA+ lymphocytes. Role of the human CD38 molecule. J. Immunol. 153, 952–959.Google Scholar
- Inoue, S., Kontani, K., Tsujimoto, N., Kanda, Y., Hosoda, N., Hoshino, S., Hazeki, O., and Katada, T. (1997). Protein-tyrosine phosphorylation by IgG1 subclass CD38 monoclonal antibodies is mediated through stimulation of the FcgammaII receptors in human myeloid cell lines. J. Immunol. 159, 5226–5232.PubMedGoogle Scholar
- Mallone, R., Ferrua, S., Morra, M., Zocchi, E., Mehta, K., Notarangelo, L.D., and Malavasi, F. (1998). Characterization of a CD38-like 78-kilodalton soluble protein released from B cell lines derived from patients with X-linked agammaglobulinemia. J. Clin. Invest. 101, 2821–2830.PubMedCrossRefGoogle Scholar
- Partida-Sanchez, S., Cockayne, D.A., Monard, S., Jacobson, E.L., Oppenheimer, N., Garvy, B., Kusser, K., Goodrich, S., Howard, M., Harmsen, A., et al. (2001). Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat. Med. 7, 1209–1216.PubMedCrossRefGoogle Scholar
- Song, E.K., Rah, S.Y., Lee, Y.R., Yoo, C.H., Kim, Y.R., Yeom, J.H., Park, K.H., Kim, J.S., Kim, U.H., and Han, M.K. (2011). Connexin-43 hemichannels mediate cyclic ADP-ribose generation and its Ca2+-mobilizing activity by NAD+/cyclic ADP-ribose transport. J. Biol. Chem. 286, 44480–44490.PubMedCrossRefGoogle Scholar