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Dangerous attraction: phagocyte recruitment and danger signals of apoptotic and necrotic cells

  • Clearance of dead cells: mechanisms, immune responses and implication in the development of diseases
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Abstract

Tissue homeostasis in metazoa requires the rapid and efficient clearance of dying cells by professional or semi-professional phagocytes. Impairment of this finely regulated, fundamental process has been implicated in the development of autoimmune diseases, such as systemic lupus erythematosus. Various studies have provided us a detailed understanding of the interaction between dying cells and phagocytes as well as the current concept that apoptotic cell removal leads to a non- or anti-inflammatory response, whereas necrotic cell removal stimulates a pro-inflammatory reaction. In contrast, our knowledge about the soluble factors released from dying cells is rather limited, although meanwhile it is generally accepted that not only the dying cell itself but also the substances liberated during cell death contribute to the process of corpse clearance and the subsequent immune response. This review article is intended as an up-to-date survey over attraction and danger signals of apoptotic, primary and secondary necrotic cells, their function as chemoattractants in phagocyte recruitment, additional effects on the immune system, and the receptors, which are engaged in this scenario.

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Abbreviations

ADAM 17:

A disintegrin and metalloproteinase 17

APC:

Antigen presenting cell

C5a:

Complement protein 5a

CARD:

Caspase recruitment domain

CLEVER-1:

Common lymphatic endothelial and vascular endothelial receptor 1

COX-2:

Cyclooxygenase-2

DAMP:

Damage associated molecular pattern

DC:

Dendritic cell

dRP S19:

Dimer of ribosomal protein S19

ELC:

EBV-induced molecule 1 ligand chemokine

EMAP II:

Endothelial monocyte-activating polypeptide II

FcRγ:

Receptor for Fc region of IgG

fMLP:

N-Formylmethionyl-leucyl-phenylalanine

GP96:

Glycoprotein 96

GPCR:

G protein coupled receptor

HBD:

Heparin binding domain

HDGF:

Hepatocyte derived growth factor

HMGB-1:

High mobility group box 1 protein

HSP:

Heat shock protein

ICAM:

Intercellular adhesion molecule

iDC:

Immature dendritic cell

IFN:

Interferon

IL:

Interleukin

IP-10:

Inducible protein of 10 kDa

iPLA2 :

Calcium-independent phospholipse A2

IRAK:

Interleukin-1 receptor-associated kinase

KC:

Keratinocyte chemoattractant

Ku:

Ku autoantigen

LOX-1:

Lectin-like oxidized low-density lipoprotein receptor

LPC:

Lysophosphatidylcholine

LPS:

Lipopolysaccharide

LTB4 :

Leukotrien B4

LTF:

Lactoferrin

MAPK:

Mitogen-activated protein kinase

MCP:

Monocyte chemotactic protein

MDC:

Macrophage-derived chemokine

MFG-E8:

Milk-fat globule EGF-factor 8

Mincle:

Macrophage-inducible C-type lectin

MIP:

Macrophage inflammatory protein

MSU:

Monosodium urate

MyD88:

Myeloid differentiation primary response gene 88

NALP3:

NACHT domain- leucine-rich repeat- and PYD-containing protein 3

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NK cell:

Natural killer cell

NOS:

NO synthase

OVA:

Ovalbumin

P2X:

Purinergic receptor X

P2Y:

Purinergic receptor Y

PARP poly:

Poly (ADP-ribose) polymerase

PBMC:

Peripheral blood mononuclear cell

PGE2 :

Prostaglandin E2

RAGE:

Receptor for advanced glycation end products

RANTES:

Regulated upon activation, normal T-cell expressed and secreted

RNP:

Ribonucleoprotein

S1P:

Sphingosin-1-phosphate

SAP130:

Spliceosome-associated polypeptide of 130 kDa

SDF-1:

Stromal cell-derived factor-1

SLE:

Systemic lupus erythematosus

SphK:

Sphingosin kinase

SR-A:

Scavenger receptor A

SREC-1:

Scavenger receptor class F member 1

SSA/Ro:

Sjoegren syndrome antigen A/autoantigen Ro

SSB/La:

Sjoegren syndrome antigen B/autoantigen La

TGase 2:

Transglutaminase 2

TGF-β:

Transforming growth factor β

TIR:

Toll/IL-1 receptor domain

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TSP-1:

Thrombospondin-1

TyrRS:

Tyrosyl tRNA synthetase

U1-70 kd:

70 kDa polypeptide of U1 small nuclear RNP

UA:

Uric acid

VCAM:

Vascular cell adhesion molecule

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Acknowledgments

We thank the members of the Wesselborg and the Herrmann lab for stimulating discussions and apologize to all colleagues in the field of engulfment and inflammation, whose work could not be cited here owing to space constraints. This work was supported by the DFG We 1801/2-4 and SFB 685.

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Authors and Affiliations

  1. Section of Molecular Gastroenterology, Department of Internal Medicine I, University of Tuebingen, Tuebingen, Germany

    Christoph Peter, Sebastian Wesselborg & Kirsten Lauber

  2. Institute for Clinical Immunology, Department for Internal Medicine 3, University Hospital Erlangen, Erlangen, Germany

    Martin Herrmann

  3. Department of Internal Medicine I, Eberhard-Karls-University, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany

    Kirsten Lauber

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  1. Christoph Peter
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  2. Sebastian Wesselborg
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Correspondence to Kirsten Lauber.

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Peter, C., Wesselborg, S., Herrmann, M. et al. Dangerous attraction: phagocyte recruitment and danger signals of apoptotic and necrotic cells. Apoptosis 15, 1007–1028 (2010). https://doi.org/10.1007/s10495-010-0472-1

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