Cross reactivity of three T cell attracting murine chemokines stimulating the CXC chemokine receptor CXCR3 and their induction in cultured cells and during allograft rejection

Recent work identified the murine gene homologous to the human T cell attra cting chemokine CXC receptor ligand 11 (CXCL11, also termed I-TAC, SCYB11, beta -R1, H174, IP-9). Here, the biological activity and expression pattern s of murine CXCL11 relative to CXCL9 (MIG) and CXCL10 (IP-10/crg-2), the ot her two CXCR3 ligands, were assessed. Calcium mobilization and chemotaxis e xperiments demonstrated that murine CXCL11 stimulated murine CXCR3 at much lower doses than murine CXCL9 or murine CXCL10. Murine CXCL11 also evoked c alcium mobilization in CHO cells transfected with human CXCR3 and was chemo tactic for CXCR3-expressing human T lymphocytes as well as for 300-19 pre-B cells transfected with human or murine CXCR3. Moreover, murine CXCL11 bloc ked the chemotactic effect of human CXCL11 on human CXCR3 transfectants. De pending on cell type (macrophage-like cells RAW264.7, J774A.1, fetal F20 an d adult dermal fibroblasts, immature and mature bone marrow-derived dendrit ic cells) and stimulus (interferons, LPS, IL-1 beta and TNF-alpha), an up t o 10,000-fold increase of CXCL9, CXCL10 and CXCL11 mRNA levels, quantified by real-time PCR, was observed. In vivo, the three chemokines are constitut ively expressed in various tissues from healthy BALB/c mice and were strong ly up-regulated during rejection of allogeneic heart transplants. Chemokine mRNA levels exceeded those of CXCR3 and IFN-gamma which were induced with similar kinetics by several orders of magnitude.