The immune response to secondary necrotic cells

Abstract

When apoptotic cells are not cleared in an efficient and timely manner, they progress to secondary necrosis and lose their membrane integrity. This results in a leakage of immunostimulatory, danger associated molecular patterns (DAMPs), similar to accidental (or primary) necrosis. However, primary necrosis is a sudden event with an inadvertent release of almost unmodified DAMPs. Secondary necrotic cells, in contrast, have gone through various modifications during the process of apoptosis. Recent research revealed that the molecules released from the cytoplasm or exposed on the cell surface differ between primary necrosis, secondary necrosis, and regulated necrosis such as necroptosis. This review gives an overview of these differences and focusses their effects on the immune response. The implications to human physiology and diseases are manifold and will be discussed in the context of cancer, neurodegenerative disorders and autoimmunity.

Donor kidney injury molecule-1 promotes graft recovery by regulating systemic necroinflammation

“…Given the essential role of KIM-1 in the phagocytic clearance of apoptotic 27 and necrotic cells in the kidney, 19 we expected that the Figure 2A) and necrotic cells (11.5 ± 1.041 vs 0.5333 ± 0.1202, P = .0005; Figure 2B) compared to mice transplanted with wild-type donor kidneys. In addition, we looked at ATN to determine the degree of graft injury.…”

“…Given the essential role of KIM-1 in the phagocytic clearance of apoptotic 27 and necrotic cells in the kidney, 19 we expected that the poor transplant outcomes associated with donor KIM-1 deficiency would be associated with increased tubular cell apoptosis and necrosis (secondary necrosis of uncleared apoptotic cells 27 ) early after transplantation. Mice transplanted with KIM-1-deficient donor kidneys exhibited increased numbers of both apoptotic (16.67 ± 3.333 vs 3.75 ± 2.394, P = .0018; Figure 2A) and necrotic cells (11.5 ± 1.041 vs 0.5333 ± 0.1202, P = .0005; Figure 2B) compared to mice transplanted with wild-type donor kidneys.…”

Estrogen promotes pro-resolving microglial behaviour and phagocytic cell clearance through the actions of annexin A1

“…Clearance of apoptotic cells by phagocytosis is critical for the maintenance of healthy tissue, as apoptotic cells that are not removed will progress to secondary necrosis and become significant inflammatory foci themselves 32 . Microglia are the principal phagocytes of the CNS and play a central role in this process, a particularly important action given the susceptibility of neurones to inflammatory damage 33 .…”

Regulation of efferocytosis as a novel cancer therapy

“…Subsequently, the membrane integrity of apoptotic cells is maintained, hence avoiding the exposure of immunogenic materials and the subsequent inflammatory responses [2]. This physiologic process, referred to as efferocytosis, efficiently removes apoptotic cells without subsequent secondary necrosis and damages [3]. Efferocytosis is induced by several physiological or pathological conditions and plays a crucial role in tissue differentiation, repair, and the resolution of inflammation [4].…”