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Pro-Inflammatory Actions of Red Blood Cell-Derived DAMPs

  • Viktória Jeney
Chapter
Part of the Experientia Supplementum book series (EXS, volume 108)

Abstract

Damage-associated molecular patterns (DAMPs) or alarmins are endogenous danger signals that are derived from damaged cells and extracellular matrix degradation, capable of triggering innate immune response to promote tissue damage repair. Hemolytic or hemorrhagic episodes are often associated with inflammation, even when infectious agents are absent, suggesting that damaged red blood cells (RBCs) release DAMPs.

Hemoglobin (Hb) composes 96% of the dry weight of RBCs; therefore upon hemolysis, tremendous amounts of Hb are released into the extracellular milieu. Hb oxidation occurs outside the protective environment of RBCs, leading to the formation of different Hb oxidation products and heme. Heme acts as a prototypic DAMP participating in toll-like receptor as well as intracellular nucleotide-binding oligomerization domain-like receptor signaling. Oxidized Hb forms also possess some inflammatory actions independently of their heme releasing capability. Non-Hb-derived DAMPs such as ATP, interleukin-33, heat shock protein 70, as well as RBC membrane-derived microparticles might also contribute to the innate immune response triggered by hemolysis/hemorrhage.

In this chapter we will discuss the inflammatory properties of RBC-derived DAMPs with a particular focus on Hb derivatives, as well as therapeutic potential of the endogenous Hb and heme-binding proteins haptoglobin and hemopexin in the prevention of hemolysis/hemorrhage-associated inflammation.

Keywords

Hemoglobin Red blood cells Inflammasome DAMPs Hemolysis Hemorrhage 

Abbreviations

ASC

Apoptosis-associated speck-like protein containing a caspase recruitment domain

ATP

Adenosine triphosphate

CO

Carbon monoxide

Cys

Cysteine

DAMPs

Damage-associated molecular patterns

FerrylHb

Ferrylhemoglobin

Hb

Hemoglobin

HO-1

Heme oxygenase-1

H2O2

Hydrogen-peroxide

Hp

Haptoglobin

Hsp

Heat shock protein

Hx

Hemopexin

ICAM-1

Intracellular adhesion molecule-1

ICH

Intracerebral hemorrhage

IL

Interleukin

LPS

Lipopolysaccharide

MetHb

Met(ferric) hemoglobin

Mhem macrophage

Hemorrhage-associated macrophage

MPs

Microparticles

MyD88

Myeloid differentiation primary response gene 88

NADPH

Nicotinamide adenine dinucleotide phosphate

NF-κB

Nuclear factor kappa B

NLR

NOD-like receptor

NLRP3

NLR family pyrin domain containing 3

NOD

Nucleotide-binding oligomerization domain

NRF2

Nuclear factor erythroid 2-related factor 2

PAMPs

Pathogen-associated molecular patterns

PPIX

Protoporphyrin IX

RBC

red blood cell

P2X7

P2X purinoceptor 7

TLR

Toll-like receptor

ROS

Reactive oxygen species

TNF-α

Tumor necrosis factor-alpha

TRIF

TIR-domain-containing adapter-inducing interferon-β

Tyr

Tyrosine

VCAM-1

Vascular cell adhesion molecule-1

Notes

Acknowledgments

This work was supported by grant from the National Research, Development and Innovation Office (NKFIH grant number: K116024).

Conflict of Interest

The author has no conflict of interest.

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Faculty of Medicine, Department of Internal MedicineUniversity of DebrecenDebrecenHungary

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