Monoclonal antibodies binding to the human neutrophil C3bi receptor have
disparate functional effects
DD Hickstein, RM Locksley, PG Beatty, A Smith, DM Stone and RK Root
Three monoclonal antibodies (MAb)--OKMI, 7C3, and 60.3-- immunoprecipitated
a common 170-kd neutrophil membrane antigen closely associated with, or
identical to, the C3bi receptor (CR3). Despite binding to a common
receptor, these antibodies displayed marked differences in their effects on
C3bi-mediated neutrophil function as assessed by the binding and ingestion
of opsonized zymosan and the subsequent triggering of the respiratory
burst. Antibody 7C3 caused a time-dependent, irreversible inhibition of the
neutrophil oxidative response to opsonized zymosan that correlated with
capping of the bound antibody. In contrast, antibody 60.3 caused an
immediate inhibition of the neutrophil oxidative response to opsonized
zymosan that required the continuous presence of exogenous antibody to
achieve the maximal inhibitory effect. Antibody OKMI demonstrated minimal
inhibition of O2- release. Despite their functional differences, binding of
either 7C3 or 60.3 led to up-regulation of new antigen, presumably from
intracellular sites as previously described using OKMI. Crossed
immunoprecipitations of radiolabeled neutrophil lysates indicated that each
MAb bound to different antigens near or within the CR3 complex. Thus three
MAb binding to the neutrophil CR3 receptor each caused receptor up-
regulation but had markedly different functional effects on the cell.
Volume 67,
Issue 4,
pp. 1054-1062,
04/01/1986
Copyright © 1986 by The American Society of Hematology
