THE TYPE OF INTERACTION WITH FC-GAMMA-R IN HUMAN MONOCYTES DETERMINESTHE EFFICIENCY OF THE GENERATION OF OXIDATIVE BURST

Receptors for the Fc fragment of IgG (Fc gamma R) have a well-document ed role in the generation of oxidative burst. It is tempting to specul ate that the type of interaction with Fc gamma R could be a mechanism of regulation of this process. Here we report on a comparative study o f the induction of oxidative burst in human monocytes activated by mea ns of different types of interaction with Fc gamma R. We studied non-p rimed monocytes obtained by centrifugal elutriation from healthy donor s. These cells were submitted to Fc gamma R interactions following two distinct models: one, using particulate material (IgG-SRBC leading to phagocytosis or resetting), and another using soluble reagents follow ed by cross-linking of the receptors (monoclonal antibodies against Fc gamma RI and Fc gamma RII and natural ligands, namely several isotype s of murine and human IgG). Phagocytosis and oxidative burst were stud ied simultaneously in the monocytes, following the methodology describ ed recently. Human non-primed monocytes were able to generate a very o bvious oxidative burst response after activation of Fc gamma R by part iculate material. The same response was observed when Fc gamma RII was blocked by monoclonal antibodies. Ingestion was not necessary for act ivation of the oxidative burst, since the model of resetting induced a level of burst generation similar to the one obtained in the phagocyt ic process. Cross-linking of Fc gamma RI by soluble reagents induced p roduction of reactive oxidative intermediates (ROI) only when the liga nd-binding site of the receptor was involved. These data lead to the c onclusion that Fc gamma R interaction with soluble or particulate mate rial induces oxidative burst in non-primed human monocytes only when t he binding site of natural ligands is involved. The type of interactio n also determines the efficiency of the generation of ROI. This fact c ould represent a regulatory mechanism.