Regulation of granulocyte apoptosis and implications for anti-inflammatory therapy

Open Access
Publisher Website
Google Scholar
Abstract
The elimination of unwanted cells is now regarded as an essential component of many normal biological programmes. These include embryonic remodelling, the removal of autoreactive thymic T cells, and the disposal of senescent enterocytes at the villus tip. Hence cell death, in particular apoptosis or “programmed cell death”, appears to be a prerequisite for life.1 In the particular example of inflammation many of the unique features of apoptosis, such as the retention of plasma membrane integrity, the loss of the cytotoxic and secretory capacity of the cell, and the ability of apoptotic cells to be recognised and phagocytically removed, suggest that this remarkable process may play a key role in limiting tissue injury and facilitating the successful resolution of inflammation.2-5 Furthermore, the ingestion of apoptotic cells by macrophages, unlike the uptake of other biological and non-biological material, fails to induce a secretory or pro-inflammatory response.6 7 Although a number of different cells within the lung have the capacity to undergo apoptosis (including the bronchial epithelial cell and type II pneumocyte8 9), the central role of the granulocyte as the primary effector cell in most forms of lung and airway wall inflammation, coupled with the huge potential for these cells to induce tissue injury if not cleared, marks the apoptotic capacity of these cells as being of particular importance in lung inflammation. Despite the considerable interest generated by the discovery that neutrophils and eosinophils undergo constitutive apoptosis when aged in vitro,2 10 a process that results in their ingestion by either …