Phagocytosis of apoptotic cells and the resolution of inflammation

Abstract

Clearance of apoptotic cells by phagocytic cells plays a significant role in the resolution of inflammation, protecting tissue from harmful exposure to the inflammatory and immunogenic contents of dying cells. Apoptosis induces cell surface changes that are important for recognition and engulfment of cells by phagocytes. These changes include alterations in surface sugars, externalization of phosphatidylserine and qualitative changes in the adhesion molecule ICAM-3. Several studies have contributed to clarify the role of the receptors on the surface of phagocytes that are involved in apoptotic cell clearance. The phagocytic removal of apoptotic cells does not elicit pro-inflammatory responses; in contrast, apoptotic cell engulfment appears to activate signals that suppress release of pro-inflammatory cytokines. Therefore, clearance of apoptotic leucocytes is implicated in the resolution of inflammation and mounting evidence suggests that defective clearance of apoptotic cells contributes to inflammatory and autoimmune diseases. Defining the ligands on apoptotic cells and the corresponding receptors on phagocytes with which they engage, is likely to lead to the development of novel anti-inflammatory pro-resolution drugs. In this article, we will review the recognition and signaling mechanisms involved in the phagocytosis of apoptotic cells as well as the role of endogenous compounds that play a relevant role in the modulation of inflammation. We will also discuss what is currently known about diseases that may reflect impaired phagocytosis and the consequences on inflammation and immune responses.

Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair

“…The liposomes had a particle size of 1.2 AE 0.3 μm for efficient uptake by macrophages ( Fig. S1) (12).…”

The Melanocortin Agonist AP214 Exerts Anti-Inflammatory and Proresolving Properties

“…42,43 Furthermore, recognition of apoptotic neutrophils exerts additional anti-inflammatory effects because it leads back to inhibit the release of pro-inflammatory mediators and activate the production of anti-inflammatory IL-10 and TGF-␤. 44 -46 Many proinflammatory mediators, such as annexin A1, glucocorticoid, and lipoxin A 4 , have been shown to produce proefferocytic effects, [47][48][49] but no data are available with respect to MC receptor agonists.…”

Transient inflammatory response induced by apoptotic cells is an important mediator of melanoma cell engraftment and growth

“…To further characterize the inflammatory response seen after injection of melan-a cells, immunohistochemistry of tissue sections was performed using a polyclonal antibody against the cytoplasmic MRP-14 antigen, which is highly expressed in neutrophils and monocytes. 16,17 As shown in Figure 2e,f, strong immunoreactivity of the anti-MRP-14 antibody suggests the presence of a great number of neutrophils and/or macrophages at the site of melan-a injection after 24 hr, demonstrating that melan-a cells undergoing rapid and intense apoptosis are accompanied by pronounced infiltration of neutrophils and macrophages.…”

“…11 Whereas increased levels of leukocyte infiltration into primary tumors are usually a good prognostic sign, 12 the presence of inflammatory cell infiltrates has been correlated with cytokine and growth factor production, which may provide a favorable microenvironment for neoplastic proliferation. [13][14][15][16] Clearance of apoptotic cells by phagocytes plays a significant role in the resolution of inflammation, 17 and although the lack of an inflammatory infiltrate is by definition a hallmark of death by apoptosis, several lines of investigation have challenged this concept. Indeed, apoptotic cells can evoke an inflammatory response depending on how apoptosis is initiated, in what cell type it occurs and whether or not particular cofactors are present.…”