Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation.

Omar Rafael Alemán,Carlos Rosales,Eileen Uribe-Querol,Nancy Mora,Ricarda Cortes-Vieyra

doi:10.1155/2016/2908034

Abstract

Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA) are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

Highlights

Neutrophils (PMN) are the most abundant leukocytes in the blood
Some reports indicated that neutrophil extracellular traps (NETs) formation was increased when microorganisms were opsonized with autologous serum and that antigenantibody complexes seemed to be capable of inducing NET formation
Neutrophils are the most abundant circulating leukocytes in mammals and they are rapidly recruited to sites of infection, where they act as the first line of defense against invading pathogens [42]

Summary

Introduction

Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN are innate immune cells that migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions [1]. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes [2, 3]. NET fibers are composed of chromatin covered with histones [7] and antimicrobial proteins derived from the neutrophil granules, such as the bactericidal/permeability-increasing protein (BPI), elastase, myeloperoxidase, lactoferrin, and metalloprotease 9 [2, 4]. The requirements for NADPH-oxidase and myeloperoxidase in NET formation differ depending on the stimulus [8, 9]. Besides their antimicrobial capacity, NETs seem to act as a physical barrier where microorganisms get trapped and prevent further spread of pathogens. NETs bind, block, and kill microorganisms extracellularly and independently of phagocytosis [10]

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Conclusion