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RIIIb Induces the Production of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor by Polymorphonuclear Neutrophils
Laboratory of Immunology, Institut de Synergie des Sciences et de la Santé, Brest University Medical School, Brest, France
We have reported that human autoantibodies reacting with the
polymorphonuclear neutrophil (PMN)-anchored Fc
RIIIb (CD16) protect
these cells from spontaneous apoptosis. In this study, we used
anti-CD16 F(ab')2 to delineate the mechanism(s) whereby
the PMN life span is extended. As documented using four methods, CD16
cross-linking impeded spontaneous apoptosis, whereas anti-CD18
F(ab')2 exerted no effect. Incubation of PMNs with
anti-CD16 prevented the up-regulation of
2
integrins, particularly CD11b, which is the
-chain of complement
receptor type 3, but also CD18, which is its
-chain, as well as
CD11a and CD11c. Anti-CD16-conditioned supernatant of PMNs diminished
the percentage of annexin V-binding fresh PMNs after another 18 h
in culture, whereas the negative control anti-CD18 had no effect.
The expression of mRNA for G-CSF and GM-CSF was induced by
anti-CD16, followed by the release of G-CSF and GM-CSF in a
dose-dependent manner. Anti-G-CSF and anti-GM-CSF mAbs abrogated
the antiapoptotic effect of the related growth factors. The delay in
apoptosis was accompanied by a down-regulated expression of
Bax, and a partial reduction of caspase-3 activity.
These data suggest an autocrine involvement of anti-CD16-induced
survival factors in the rescue of PMNs from spontaneous apoptosis.
Thus, apoptosis of aged PMNs can be modulated by signaling through
Fc
RIIIb, which may occur in patients with PMN-binding
anti-Fc
RIIIb autoantibodies.
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