**Abstract**

Neutrophils, the most abundant leukocytes in blood, are relevant cells of both the innate and the adaptive immune system. Immunoglobulin (Ig) G antibody molecules are crucial activators of neutrophils. IgGs identify many types of pathogens via their two Fab portions and are in turn detected through their Fc portion by specific Fcγ receptors (FcγRs) on the membrane of neutrophils. Thus, antibodies bring the specificity of the adaptive immune response to the potent antimicrobial and inflammatory functions of neutrophils. Two types of FcγRs with several polymorphic variants exist on the human neutrophil. These receptors are considered to be redundant in inducing cell responses. Yet, new evidence presented in recent years on how the particular IgG subclass and the glycosylation pattern of the antibody modulate the IgG–FcγR interaction has suggested that a particular effector function may in fact be activated in response to a specific type of FcγR. In this chapter, we describe the main types of FcγRs on neutrophils and our current view on how particular FcγRs activate various signaling pathways to promote unique effector cell functions, including phagocytosis, activation of integrins, nuclear factor activation, and formation of neutrophil extracellular traps (NETs).

**Keywords:** neutrophil, phagocytosis, degranulation, NETs, antibody, Fc receptors, integrins, NF-κB

## **1. Introduction**

Neutrophils are the most abundant cell type in human blood. They are produced in the bone marrow and then released into the circulation. At sites of infection or inflammation, neutrophils migrate to tissues, where they complete their functions. Finally, neutrophils die by apoptosis and are eliminated by macrophages. Neutrophils are an essential part of the innate immune system [1], with significant antimicrobial functions, including phagocytosis, degranulation, and the formation of neutrophil extracellular traps (NETs). These antimicrobial functions were believed to be the only goal of neutrophils. However, it has recently become clear that neutrophils display many functional responses that go beyond the simple killing of microorganisms. Neutrophils produce cytokines [2] and other inflammatory factors [3] that regulate the whole immune system [4, 5]. Consequently, neutrophils are also key effector cells of the adaptive immune system.

Immunoglobulin (Ig) G antibody molecules are an essential part of the adaptive immune system. IgGs recognize antigens via their two Fab portions and are in turn linked through their Fc portion to specific Fcγ receptors (FcγRs) on the membrane of leukocytes [6, 7]. In this way, antibodies function as a bridge between the specific adaptive immune response and the potent innate immune functions of leukocytes. In the human neutrophil, two types of FcγR exist. Thus, antibodies are important activators of neutrophils. The Fcγ receptors on the neutrophil are considered to be redundant in inducing cell responses [8, 9]. However, recent findings on how a particular IgG subclass and the glycosylation pattern of the antibody regulate the IgG–FcγR interaction suggest that a particular effector function may in fact be activated in response to a specific type of FcγR. It is the purpose of this chapter to describe the FcγRs on human neutrophils and present our current view of how particular FcγRs activate various signaling pathways to promote unique effector cell functions.
