Pro-Inflammatory Actions of Red Blood Cell-Derived DAMPs

  • Viktória JeneyEmail author
Part of the Experientia Supplementum book series (EXS, volume 108)


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.


Hemoglobin Red blood cells Inflammasome DAMPs Hemolysis Hemorrhage 



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


Adenosine triphosphate


Carbon monoxide




Damage-associated molecular patterns






Heme oxygenase-1






Heat shock protein




Intracellular adhesion molecule-1


Intracerebral hemorrhage






Met(ferric) hemoglobin

Mhem macrophage

Hemorrhage-associated macrophage




Myeloid differentiation primary response gene 88


Nicotinamide adenine dinucleotide phosphate


Nuclear factor kappa B


NOD-like receptor


NLR family pyrin domain containing 3


Nucleotide-binding oligomerization domain


Nuclear factor erythroid 2-related factor 2


Pathogen-associated molecular patterns


Protoporphyrin IX


red blood cell


P2X purinoceptor 7


Toll-like receptor


Reactive oxygen species


Tumor necrosis factor-alpha


TIR-domain-containing adapter-inducing interferon-β




Vascular cell adhesion molecule-1



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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