Stromal cell-derived factor 1 alpha-induced chemotaxis in T cells is mediated by nitric oxide signaling pathways

Stromal cell-derived factor l alpha (SDF1 alpha) and its cognate chemokine receptor CXCR4 act as potent chemoattractants and regulate trafficking and homing of hematopoietic progenitor cells and lymphocytes. However, the mole cular mechanisms regulating SDF1 alpha -driven cell migration are not well defined. In this study, we have explored the roles of the second messenger NO and the transcription factor NF-kappaB in SDF1 alpha -induccd T cell mig ration. SDF1 alpha treatment of Jurkat T cells increased the activity of NO synthase, which catalyzes the generation of NO, We observed that pretreatm ent of Jurkat cells or activated PBLs with several NO donors significantly enhanced the SDF1 alpha -induced migration, whereas various inhibitors of N O synthase markedly abrogated the chemotactic response in a concentration-d ependent manner. Furthermore, we observed that inhibitors of the transcript ion factor NF-kappaB, which is linked to NO signaling pathways, also signif icantly blocked the SDF1 alpha -induced chemotactic response. However, thes e compounds did not have a significant effect on SDF1 alpha -induced mitoge n-activated protein kinase activity. In addition, the MAP/Erk kinase kinase inhibitor PD98059 did not abrogate SDF1 alpha -induced chemotaxis. AKT, wh ich has been shown to mediate NO production, was also phosphorylated upon S DF1 alpha stimulation. These studies suggest that NO-related signaling path ways may mediate SDF1 alpha -induced chemotaxis, but not mitogen-activated protein kinase activation.