Neuroblastoma cell-mediated leukocyte chemotaxis: Lineage-specific differentiation of interleukin-8 expression

To determine whether neural crest-derived neuroblastoma cells may release cytokines which regulate the function of leukocytes, we found that neuroblastoma (HTB−11) cells did not constitutionally express IL−1β, TNFα, or IL−8 mRNA. However, TNFα, which induced HTB−11 cells to differentiate to perineurium-like cells, induced expression of IL−8 mRNA in a dose- and time- dependent fashion. In contrast, pentoxifylline (1 mM), which promoted HTB-11 cells to differentiate to polygonal neuron-like cells, did not induce IL−8 mRNA expression. As determined by enzyme-linked immunoassay, high levels of IL-8 were detectable in the culture supernatants from TNFα-treated neuroblastoma cells, but not pentoxifylline-treated neuroblastoma cells (19.60 ± 2.34 vs 0.10 ± 0.06 ng/ml). Culture supernatants obtained from TNFα-treated neuroblastoma cells induced chemotaxis of neutrophils and lymphocytes that was significantly blocked by anti-IL−8 neutralizing antibodies. Detection of a leukocyte chemotactic factor was not observed in the culture supernatants from pentoxifylline-treated cells. These results suggest that neural crest-derived perineurium-like cells, but not neuron- like cells, may release a leukocyte chemotactic factor or factors such as IL− 8 which could be involved in leukocyte recruitment seen in inflammatory diseases affecting peripheral nerves.