Cross-Linking of Human FcγRIIIb Induces the Production of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor by Polymorphonuclear Neutrophils

Abstract

We have reported that human autoantibodies reacting with the polymorphonuclear neutrophil (PMN)-anchored FcγRIIIb (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 β2 integrins, particularly CD11b, which is the α-chain of complement receptor type 3, but also CD18, which is its β-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 FcγRIIIb, which may occur in patients with PMN-binding anti-FcγRIIIb autoantibodies.

Chlamydia pneumoniae Multiply in Neutrophil Granulocytes and Delay Their Spontaneous Apoptosis

“…Although apoptosis is an intrinsic cell process, it can also be modulated by cytokines such as GM-CSF and IL-8, which were both shown to delay the spontaneous apoptosis of PMN in a dosedependent fashion (17,53). Although upon stimulation PMN themselves are able to secrete both these antiapoptotic cytokines, production of GM-CSF was not observed after Cp infection.…”

Elevated Serum Granulocyte Colony-Stimulating Factor Levels in Patients With Active Phase of Sweet Syndrome and Patients With Active Behçet Disease

“…13 Granulocyte colony-stimulating factor is a hematopoietic growth factor that increases the number of peripheral neutrophils and active mature neutrophils. 14,15 In steady-state hematopoiesis, G-CSF regulates the level of neutrophils in bone marrow and blood and is critical for the survival of granulocytic cells. The factor strongly influences neutrophil function by stimulating production, activation, maturation, and chemotaxis of granulocytes.…”

Cross-talk between Fc receptors and integrins

“…Some studies involving protein phosphorylation and protein redistribution in which either receptor has been stimulated independently, demonstrated that each receptor generates different intracellular signals [39]. In addition, ligation of Fc␥RIIIB promotes an anti-apoptotic phenotype via the synthesis of granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) [40]. This finding is not replicated by the cross-linking of ␤2 integrins.…”