NEUROBLASTOMA CELL-MEDIATED LEUKOCYTE CHEMOTAXIS - LINEAGE-SPECIFIC DIFFERENTIATION OF INTERLEUKIN-8 EXPRESSION

To determine whether neural crest-derived neuroblastoma cells may rele ase cytokines which regulate the function of leukocytes, we found that neuroblastoma (HTB-11) cells did not constitutionally express IL-1 be ta, TNF alpha, or IL-8 mRNA. However, TNF alpha, which induced HTB-11 cells to differentiate to perineurium-like cells, induced expression o f IL-8 mRNA in a dose- and time-dependent fashion. In contrast, pentox ifylline (1 mM), which promoted HTB-11 cells to differentiate to polyg onal neuron-like cells, did not induce IL-8 mRNA expression. As determ ined by enzyme-linked immunoassay, high levels of IL-8 were detectable in the culture supernatants from TNF alpha-treated neuroblastoma cell s, but not pentoxifylline-treated neuroblastoma cells (19.60 +/- 2.34 vs 0.10 +/- 0.06 ng/ml). Culture supernatants obtained from TNF alpha- treated neuroblastoma cells induced chemotaxis of neutrophils and lymp hocytes that was significantly blocked by anti-IL-8 neutralizing antib odies. Detection of a leukocyte chemotactic factor was not observed in the culture supernatants from pentoxifylline-treated cells. These res ults suggest that neural crest-derived perineurium-like cells, but not neuron-like cells, may release a leukocyte chemotactic factor or fact ors such as IL-8 which could be involved in leukocyte recruitment seen in inflammatory diseases affecting peripheral nerves. (C) 1994 Academ ic Press, Inc.