Monoclonal antibody to human IgG Fc receptors. Cross-linking of receptors induces lysosomal enzyme release and superoxide generation by neutrophils.
The monoclonal antibody KuFc79 binds to a determinant on the Fc receptors (Fc gamma R) of human leukocytes. We examined the biologic effects of the interaction of this antibody with Fc gamma R on human neutrophils (PMNL). The univalent Fab fragment of KuFc79 inhibits the formation of rosettes with IgG-sensitized sheep erythrocytes by as much as 91.7%. In other experiments in which PMNL were washed after exposure to Fab of KuFc79, phagocytosis of IgG-sensitized sheep erythrocytes was inhibited by 36%. Fab fragments of other mouse IgG2b monoclonal proteins did not have these effects. When PMNL are exposed to coverslips coated with univalent Fab fragments of this antibody, the Fc gamma R are removed from the surface of the PMNL. Under these conditions, rosetting could be inhibited by 85.4%. We examined cross-linking of receptor bound monoclonal antibody or its Fab fragment by either Protein A or F(ab')2 of an anti-mouse Ig. As much as 31.7% of beta-glucuronidase, a marker for lysosomal enzymes, is specifically released by cross-linking the Fc gamma R on PMNL. The generation of O2- is also induced by specifically cross-linking Fc gamma R with Fab and anti-Fab. The data constitute the first formal demonstration that cross-linking of Fc gamma R on PMNL leads to enzyme release and superoxide generation.
Willis
H E
HE
Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Browder
B
B
Feister
A J
AJ
Mohanakumar
T
T
Ruddy
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008247:Lysosomes / Q000201:enzymology*; D009504:Neutrophils / Q000502:physiology*; D010587:Phagocytosis; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D012397:Rosette Formation; D013481:Superoxides / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D011961:Receptors, Fc; D017452:Receptors, IgG; D013481:Superoxides