MONOCYTE FC-GAMMA RECEPTOR CROSS-LINKING INDUCES IL-8 PRODUCTION

In response to bacterial cell wall products such as LPS, monocytes pro duce IL-8, a powerful neutrophil chemotaxin. However, in the absence o f bacterial pathogens, immune complex-mediated diseases such as rheuma toid arthritis are associated with hign levels or IL-8 In monocyte-ric h compartments. Since it is known that IgG-containing immune complexes can recruit neutrophils via an Fc gamma R-dependent process, we hypot hesized that cross-linking of monocyte Fc gamma receptors may induce I L-8. To test this hypothesis, peripheral blood mononuclear cells were evaluated for IL-8 induction in response to immobilized LPS-free poole d human IgG. Immobilized IgG, but not soluble IgG, induced IL-8 in a d ose-dependent manner (p < 0.05, r = 0.99). This induction corresponded with an up-regulation in IL-8 steady state mRNA levels that peaked at 4 h. The released IL-8 was functional, since supernatants induced con centration-dependent neutrophil migration that was inhibited by a mono clonal anti-IL-8 Ab. Evaluation of purified monocytes for IL-8 product ion, as well as FAGS analysis of IgG-stimulated PBMC preparations, dem onstrated that monocytes are the principal IL-8 producer cell. Thus, m onocyte Fc gamma R crosslinking induces biologically active IL-8, whic h may participate in the pathogenesis of immune complex-mediated disea ses.