Full text loading...
Chapter 21 : Recognition and Removal of Apoptotic Cells
Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase
This chapter discusses the recognition of apoptotic cells by phagocytes, the mechanisms of apoptotic cell phagocytosis (efferocytosis), and some of the consequences of this recognition. It illustrates, with a few nonexhaustive examples, some of the possibilities for contribution of apoptotic cell recognition and/or its mechanisms to host-parasite interrelationships. In viable cells, phosphatidylserine (PS) is generally located on the inner leaflet of the plasma membrane, which is also enriched for phosphatidylethanolamine, whereas sphingomyelin is localized to the outer leaflet along with most of the phosphatidylcholine (PC). Under certain circumstances, activation of cells leads to increased flip-flop and, as a consequence, exposure of PS. Recent studies have implicated calreticulin as a ligand on apoptotic cells that can be recognized and contributes to their removal. The possibility that thrombospondin (TSP) can act as a glue to hold everything together is intriguing. The key feature of apoptotic cell removal is the ability of phagocytes to distinguish between living versus apoptosing, or dying, cells. The general conclusion from this discussion of receptors and bridge molecules is that recognition of apoptotic cells is a highly redundant process. Much work has been carried out on the signal pathways involved in uptake of apoptotic cells. The authors present a few examples to illustrate the potential for, and to raise questions about, other possible interactions between parasites and apoptotic cell recognition, ingestion, and consequences.
Macropinocytosis, phagocytosis, and uptake of apoptotic cells (efferocytosis). The proposed tether-and-tickle mechanism ( Hoffmann et al., 2001 ) for apoptotic cell uptake is depicted with ingestion into spacious phagosomes. (With thanks to Aimee deCathelineau.)
Proposed mechanisms by which CD47 serves as a “don’t eat me” signal for viable cells, and which are inactivated when the cells become apoptotic. Ligation of SIRPα by CD47 on the viable cell activates inhibitory tyrosine phosphatases (SHPs) that block uptake signal pathways. Downregulation and/or redistribution of CD47 on apoptotic cells releases this inhibition and allows the uptake signaling to proceed. (From Gardai et al., 2006 .)
Synopsis of possible signaling pathways associated with engulfment of apoptotic cells in C. elegans and in mammals. PSRS, phosphatidylserine recognition structure, i.e., as yet unidentified phosphatidylserine receptors. (From Gardai et al., 2006 .)