Fcγ receptors exhibit different phagocytosis potential in human neutrophils

Rivas-Fuentes, Selma; García‐García, Erick; Nieto-Castañeda, Georgina; Rosales, Carlos

doi:10.1016/j.cellimm.2010.03.006

Cited by 45 publications

(37 citation statements)

References 35 publications

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“…These kinases are not only known to be key mediators of FcgR signaling, but they are also required for integrin signaling in neutrophils (58,90,91) and thus fit to our model that FcgRIIIB signals in association with Mac-1. Syk pathways have also been shown to be involved in sIC-induced activation of neutrophils and NET formation (11,44,92). Syk deficiency or blocking of Syk hinders FcgR-mediated NET formation in response to sICs (11,44,93) and, additionally, protects mice almost completely from disease development in a collagen Ab-induced arthritis model (44).…”

Section: Discussionmentioning

confidence: 99%

Immobilized Immune Complexes Induce Neutrophil Extracellular Trap Release by Human Neutrophil Granulocytes via FcγRIIIB and Mac-1

Behnen

Leschczyk

Möller

et al. 2014

The Journal of Immunology

217

191

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Canonical neutrophil antimicrobial effector mechanisms, such as degranulation, production of reactive oxygen species, and release of neutrophil extracellular traps (NETs), can result in severe pathology. Activation of neutrophils through immune complexes (ICs) plays a central role in the pathogenesis of many autoimmune inflammatory diseases. In this study, we report that immobilized ICs (iICs), which are hallmarks of several autoimmune diseases, induce the release of NETs from primary human neutrophils. The iIC-induced NET formation was found to require production of reactive oxygen species by NADPH oxidase and myeloperoxidase and to be mediated by FcγRIIIb. Blocking of the β2 integrin macrophage-1 Ag but not lymphocyte function–associated Ag-1 abolished iIC-induced NET formation. This suggests that FcγRIIIb signals in association with macrophage-1 Ag. As intracellular signaling pathways involved in iIC-induced NET formation we identified the tyrosine kinase Src/Syk pathway, which downstream regulates the PI3K/Akt, p38 MAPK, and ERK1/2 pathways. To our knowledge, the present study shows for the first time that iICs induce NET formation. Thus, we conclude that NETs contribute to pathology in autoimmune inflammatory disorders associated with surface-bound ICs.

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Section: Discussionmentioning

confidence: 99%

Immobilized Immune Complexes Induce Neutrophil Extracellular Trap Release by Human Neutrophil Granulocytes via FcγRIIIB and Mac-1

Behnen

Leschczyk

Möller

et al. 2014

The Journal of Immunology

217

191

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“…In addition, when the major cell response of neutrophils, arguably phagocytosis, was examined, FcγRIIA was the predominant FcγR mediating this response. FcγRIIIB contribution to phagocytosis was minimal [78]. In complete contrast, FcγRIIIB signaling to the neutrophil nucleus was much more efficient than FcγRIIA signaling.…”

Section: Each Fcγr Initiates Particular Signaling Pathways That Lead mentioning

confidence: 85%

Fc receptors: Cell activators of antibody functions

Rosales¹,

Uribe‐Querol²

2013

ABB

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At the onset of an infection early defense systems, such as complement, get into action. Specialized leukocytes (white blood cells) of the innate immune system, including monocytes, macrophages, and neutrophils also participate as a first line of defense against infections. These early responses are rapid but not very specific and are usually not enough to clear completely many infections. The adaptive immune system is also needed to finish the job against many microorganisms. Antibody molecules, produced during the adaptive immune response, are crucial for preventing recurrent infections. Although, IgG antibodies are essential for controlling infections, these molecules do not directly damage the microorganisms they recognize. Today, it is established that leukocytes of the innate immune system are responsible for the protective effects of these antibodies. IgG molecules bind to their cognate antigens and are in turn recognized by specific receptors (Fcγ receptors) on the membrane of leukocytes. Crosslinking these receptors on the surface of leukocytes leads to activation of several effector cell functions. These effector functions are geared toward the destruction of microbial pathogens and the induction of an inflammatory state that is beneficial during infections. However, in autoimmune diseases, antibodies can direct these effector functions against normal tissues and cause severe tissue damage. In recent years, several factors that can modulate the IgG-FcγR interaction have been elucidated. In this review, we describe the main types of Fcγ receptors, and our current view of how antibody variants interact with these receptors to initiate different cell responses. In addition, new findings on the signaling role of individual Fcγ receptors are also discussed.

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“…These results indicate that the contribution of Fc␥RIIIb to the response to HA-IgG or immune complexes is not only important but also distinct from that of Fc␥RIIa. In this context, a recent publication has shown that Fc␥RIIIb but not Fc␥RIIa activates a signaling pathway leading to ERK phosphorylation in nucleus (52).…”

Section: Discussionmentioning

confidence: 99%

FcγRIIIb Triggers Raft-dependent Calcium Influx in IgG-mediated Responses in Human Neutrophils

Marois¹,

Paré

Vaillancourt

et al. 2011

Journal of Biological Chemistry

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Human neutrophils constitutively express a unique combination of Fc␥Rs, namely Fc␥RIIa and Fc␥RIIIb. Numerous lines of evidence support the concept that these Fc␥Rs generate only partially characterized intracellular signals. However, despite the fact that both receptors are likely to be engaged simultaneously in a physiological setting, no recent publications have investigated the distinct, although partially convergent, results of their joint activation in IgG-dependent responses. To examine the significance of the co-expression of Fc␥RIIa and Fc␥RIIIb on human neutrophils, we analyzed the neutrophil responses to stimuli that engage these Fc␥Rs, namely the phagocytosis of human IgG-opsonized zymosan and the responses to heat-aggregated IgGs. Blocking antibodies to either Fc␥R significantly decreased the phagocytic index and the stimulated production of superoxide anions. Both receptors are required for optimal IgG-dependent responses by human neutrophils. On the other hand, only blocking antibodies to Fc␥RIIIb, but not to Fc␥RIIa, inhibited the mobilization of calcium in response to heat-aggregated IgGs. Furthermore, phagocytosis of IgG-opsonized zymosan by human neutrophils required an extracellular influx of calcium that was blocked only by antibodies against Fc␥RIIIb. We also observed that this calcium influx as well as the IgG-dependent phagocytosis were dependent on the integrity of the plasma membrane detergent-resistant microdomains to which both isoforms were recruited following stimulation by heat-aggregated IgGs. These data clarify the mechanisms that regulate the Fc␥Rs constitutively expressed on human neutrophils, describe a specific contribution of Fc␥RIIIb at the level of the mobilization of calcium, and provide evidence for a crucial role of detergent-resistant microdomains in this process.

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Fcγ receptors exhibit different phagocytosis potential in human neutrophils

Cited by 45 publications

References 35 publications

Immobilized Immune Complexes Induce Neutrophil Extracellular Trap Release by Human Neutrophil Granulocytes via FcγRIIIB and Mac-1

Immobilized Immune Complexes Induce Neutrophil Extracellular Trap Release by Human Neutrophil Granulocytes via FcγRIIIB and Mac-1

Fc receptors: Cell activators of antibody functions

FcγRIIIb Triggers Raft-dependent Calcium Influx in IgG-mediated Responses in Human Neutrophils

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