MONOCYTE IL-8 RELEASE IS INDUCED BY 2 INDEPENDENT FC-GAMMA-R-MEDIATEDPATHWAYS

Cross-linking of PBMC and monocyte Fc gamma R on immobilized IgG stimu lates IL-8 release. We used immobilized anti-Fc gamma R Abs to determi ne which of the three surface Fc gamma R regulated this IL-8 secretion . Fc gamma RIII cross-linking stimulated PBMC to release 5 times more IL-8 than did either Fc gamma RI or Fc gamma RII clustering(p=0.001) a nd stimulated 77% more IL-8 release from PBMC than that from purified monocytes (p=0.001). In contrast, only Fc gamma RI cross-linking signi ficantly induced monocytes to release IL-8 (p=0.05). Since purified ly mphocytes release little IL-8 in response to immobilized IgG or anti-F c gamma RIII Abs, we hypothesized that lymphocyte Fc gamma R cross-lin king augmented monocyte IL-8 release. Supernatants from IgG- or Fc gam ma RIII-stimulated lymphacytes induced monocytes to release more IL-8 than lymphocytes incubated on plastic alone (p=0.002 and p=0.003, resp ectively). THP-1 cells, which do not produce IL-8 in response to Fc ga mma R cross-linking, also released IL-8 in response to supernatants fr om IgG- or Fc gamma RIII-stimulated lymphocytes, suggesting that the s upernatant activity was not soluble immune complexes. The IL-8-stimula ting activity was heat labile, suggesting that the activity is a prote in, However, we could not reproduce or block this activity using recom binant cytokines or neutralizing anti-cytokine Abs. Thus, monocyte IL- 8 is stimulated directly through Fc gamma RI cross-linking and indirec tly through an Fc gamma RIII-stimulated soluble lymphocyte factor.