Apoptósis De Neutrófilos

Review

Innate
Immunity

Journal of

J Innate Immun 2010;2:216–227
DOI: 10.1159/000284367

Received: November 4, 2009
Accepted after revision: December 15, 2009
Published online: February 11, 2010

Neutrophil Apoptosis: Relevance to
the Innate Immune Response and
Inflammatory Disease
Sarah Fox Andrew E. Leitch Rodger Duffin Christopher Haslett
Adriano G. Rossi
MRC Centre forInflammation Research, The Queen’s Medical Research Institute, University of
Edinburgh Medical School, Edinburgh, UK

Key Words
Apoptosis Inflammation Neutrophils

advances in mechanistic understanding of apoptotic pathways and their therapeutic manipulation in appropriate and
excessive innate immune responses.
Copyright © 2010 S. Karger AG, Basel

Abstract
Neutrophils are the mostabundant cell type involved in the
innate immune response. They are rapidly recruited to sites
of injury or infection where they engulf and kill invading microorganisms. Neutrophil apoptosis, the process of programmed cell death that prevents the release of neutrophil
histotoxic contents, is tightly regulated and limits the destructive capacity of neutrophil products to surrounding tissue. Thesubsequent recognition and phagocytosis of apoptotic cells by phagocytic cells such as macrophages is central
to the successful resolution of an inflammatory response
and it is increasingly apparent that the dying neutrophil itself exerts an anti-inflammatory effect through modulation
of surrounding cell responses, particularly macrophage inflammatory cytokine release. Apoptosis may be delayed,induced or enhanced by micro-organisms dependent on their
immune evasion strategies and the health of the host they
encounter. There is now an established field of research
aimed at understanding the regulation of apoptosis and its
potential as a target for therapeutic intervention in inflammatory and infective diseases. This review focuses on the
physiological regulation of neutrophil apoptosiswith respect to the innate immune system and highlights recent

© 2010 S. Karger AG, Basel
Fax +41 61 306 12 34
E-Mail karger@karger.ch
www.karger.com

Accessible online at:
www.karger.com/jin

Introduction

Neutrophils are the most abundant cells of the innate
immune system and are major players in the body’s fight
against infection. Neutrophils release a cytotoxic and
proteolyticcocktail that allows effective killing of invading micro-organisms. Neutrophils and their armamentarium contribute significantly to the inflammatory response in normal physiology and there are important
regulatory mechanisms that allow limitation and resolution of this response [1, 2]. Apoptosis, a programmed cell
death that occurs to conserve toxic neutrophil contents,
is one such mechanism.The apoptotic cell undergoes
several characteristic alterations (fig. 1), including alteration of cell surface markers (e.g. increased expression of
phosphatidylserine) that help phagocytes, such as macrophages, to clear them [3]. Apoptosis and the subse-

S. Fox and A.E. Leitch contributed equally.

Dr. Sarah Fox
MRC Centre for Inflammation Research
The Queen’s Medical Research Institute,University of Edinburgh Medical School
47 Little France Crescent, Edinburgh EH16 4TJ (UK)
Tel. +44 131 242 6659, Fax +44 131 242 6578, E-Mail sfox1 @ staffmail.ed.ac.uk

0–1 h

a

2–4 h

c

b
4–8 h

e

d
8–10 h

f

10–12 h

g

Fig. 1. Demonstration of neutrophil apoptosis by live-cell imaging
using confocal microscopy. Neutrophil apoptosis induced by thecyclin-dependent kinase inhibitor R-roscovitine. Neutrophil with
intact mitochondria fluorescing red (a). Neutrophil has rounded
up (b) before blebbing occurs (c) and mitochondrial dissipation
with green fluorescence throughout the cytoplasm (d). Annexin-

V binding to exposed phosphatidylserine residues is shown by
green fluorescence at cell periphery (e) followed by secondary necrosis with PI entering...