Fate of macrophages once having ingested apoptotic cells: Lymphatic clearance or in situ apoptosis?

Abstract

Neutrophil and macrophage kinetics at the inflamed site differ markedly [1, 2]. Unlike neutrophils, many organs and tissues have a population of resident macrophages, hence these cells have a different baseline at the outset of inflammation. Resident macrophages are a key population in the initiation of local inflammation [3]. Neutrophils influx rapidly early in the acute inflammatory event, while resident tissue macrophages may actually decline in numbers due to a process known as the macrophage disappearance reaction (MDR) [4]. Like neutrophils, inflammatory monocytes migrate in from the blood stream, although this lags somewhat behind the insurgence of neutrophils. These monocytes mature locally into inflammatory macrophages, although their activation state may alter over the course of the inflammatory process [5, 6]. Neutrophil numbers peak earlier than macrophages. Their decline can be due to necrosis, apoptosis and subsequent phagocytosis, or progressing to secondary necrosis if phagocytosis of apoptotic cells fails [7]. Neutrophils may be able to efflux away from the inflamed site, for example back into the blood stream, or, with pulmonary inflammation for example, they can migrate into the airway lumen [8]–[10]. It appears, however, that their main fate is to undergo apoptosis locally as shown in a number of models and in vivo settings [7, 11]. In normally resolving inflammation, macrophages phagocytose the apoptotic neutrophils and their numbers then decline allowing the tissue to return to normal structure and function [12]–[14]. This chapter examines macrophage clearance in the resolution of inflammation.