Molecular and subcellular mechanisms of vital macrophage extracellular trap formation.

Macrophage extracellular traps (METs) are a poorly understood process beneficial for infection control but detrimental in inflammation, autoimmunity and cancer. Our research shows that viable macrophages release METs even when plasma membrane lysis is blocked. We demonstrate, for the first time, that nuclear DNA is extruded directly into the cytoplasm through Gasdermin D pores on the nuclear envelope.

High‑dose X‑ray irradiation induces NETosis via the eCIRP/TREM‑1 axis in mouse neutrophils.

High‑dose ionizing radiation induces multiple types of tissue injuries, including hematopoietic dysfunction characterized by neutropenia. Neutrophil extracellular traps (NETs) released during NETosis may contribute to the neutropenia, and subsequent infection and inflammation. Triggering receptor expressed on myeloid cells‑1 (TREM‑1) is one of receptors responsible for NET formation and extracellular cold‑inducible RNA‑binding protein (eCIRP) is a ligand for the TREM‑1 receptor.

Critical Role of IL1R2-ENO1 Interaction in Inhibiting Glycolysis-Mediated Pyroptosis for Protection Against Lethal Sepsis.

Immune cell metabolic reprogramming toward glycolysis is vital for sepsis defense. While interleukin 1 receptor 2 (IL1R2) acts as a decoy receptor for IL1α/β, its potential impact on cell metabolism and death during sepsis remains unclear. This study observed elevated plasma soluble IL1R2 (sIL1R2) levels in septic patients and mice.

A multi-damage-associated molecular pattern targeting opsonic peptide attenuates gut ischemia/reperfusion-induced lung injury.

Background: Gut ischemia-reperfusion induces the release of damage-associated molecular patterns (DAMPs), exacerbating inflammation and organ injury and reducing survival. We recently developed a multi-damage-associated molecular pattern scavenging molecule, named opsonic peptide 18, which promotes the clearance of multiple damage-associated molecular patterns by phagocytes. The present study aims to investigate the therapeutic potential of opsonic peptide 18 in gut ischemia-reperfusion-induced lung injury.

A novel molecule targeting neutrophil-mediated B-1a cell trogocytosis attenuates sepsis-induced acute lung injury.

Sepsis is a dysregulated immune response to infection. B-1a cells play a crucial role in maintaining immuno-physiologic homeostasis. Sialic acid-binding immunoglobulin-like lectin G (Siglec-G) regulates B-1a cell's behavior and function.

Identification of a multiple DAMP scavenger mimicking the DAMP-binding site of TLR4 to ameliorate lethal sepsis.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Current treatments are limited to source control and supportive care, underscoring the urgent need for novel therapeutic interventions. Endogenous molecules released from stressed or damaged cells, known as damage-associated molecular patterns (DAMPs), exacerbate inflammation, organ injury, and mortality in sepsis.

Anti-DAMP therapies for acute inflammation.

Shock, affecting a third of intensive care patients, remains a highly fatal condition despite advances in critical care, irrespective of its etiology. Cellular injury, central to shock pathophysiology, triggers the release of damage-associated molecular patterns (DAMPs), such as extracellular cold-inducible RNA-binding protein (eCIRP), high-mobility group box 1 (HMGB1), histones 3 and 4, and adenosine triphosphate (ATP). These molecules are confined within cells under normal conditions and perform essential physiological functions.

CD300ld promotes neutrophil bacterial phagocytosis in sepsis.

Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. Neutrophils act as first line of defense against infection, but their function can become impaired in sepsis. CD300 antigen-like family member d (CD300ld), predominantly expressed on neutrophils, associates with Fc receptor common gamma-chain (FcRγ chain), a component vital for phagocytosis.

A MULTIPLE DAMAGE-ASSOCIATED MOLECULAR PATTERN-SCAVENGING COMPOUND OP18 ATTENUATES HEPATIC ISCHEMIA/REPERFUSION INJURY.

Introduction: Hepatic ischemia-reperfusion (I/R) can cause further liver injury through a cascade of complex cellular events. Damage-associated molecular patterns (DAMPs) released from stressed or damaged cells in the liver contribute to this pathology, leading to hyperinflammation, organ tissue damage, and high mortality. We have developed a novel compound, Opsonin Peptide 18, which exhibits strong binding affinity for multiple DAMPs, including extracellular cold-inducible RNA-binding protein, high-mobility group box 1, and histone H3, thereby enhancing the clearance of those DAMPs by phagocytic cells.

Extracellular Cold-Inducible RNA-Binding Protein: Progress from Discovery to Present.

Extracellular cold-inducible RNA-binding protein (eCIRP) is a critical damage-associated molecular pattern (DAMP) that drives inflammation and tissue injury in hemorrhagic and septic shock, and has emerged as a promising therapeutic target. Since then, extensive research using preclinical models of diseases and patient materials has explored eCIRP's role in driving inflammatory responses and its potential as a biomarker. The main objective of this comprehensive review is to provide a detailed overview of eCIRP, covering its discovery, role in disease pathophysiology, mechanisms of release and action, potential as a biomarker, and therapeutic strategies targeting eCIRP in preclinical models of inflammatory and ischemic diseases.

Milk fat globule-epidermal growth factor-VIII-derived oligopeptide 3 (MOP3) attenuates inflammation and improves survival in hepatic ischemia/reperfusion injury.

Introduction: Hepatic ischemia/reperfusion injury is a severe clinical condition leading to high mortality as the result of excessive inflammation, partially triggered by released damage-associated molecular patterns. Extracellular cold-inducible RNA-binding protein is a new damage-associated molecular pattern. Current clinical management of hepatic ischemia/reperfusion injury is limited to supportive therapy, necessitating the development of novel and effective treatment strategies.

The Novel MFG-E8-derived Oligopeptide, MOP3, Improves Outcomes in a Preclinical Murine Model of Neonatal Sepsis.

Introduction: Neonatal sepsis is a devastating inflammatory condition that remains a leading cause of morbidity and mortality. Milk fat globule-EGF-factor VIII (MFG-E8) is a glycoprotein that reduces inflammation, whereas extracellular cold-inducible RNA binding protein (eCIRP) worsens inflammation. This study aimed to determine the therapeutic potential of a novel MFG-E8-derived oligopeptide 3 (MOP3) designed to clear eCIRP and protect against inflammation, organ injury, and mortality in neonatal sepsis.

B-1a cells scavenge NETs to attenuate sepsis.

B-1a cells, a regulatory subset of B lymphocytes, produce natural IgM and interleukin-10. Neutrophil extracellular traps (NETs) play a crucial role in pathogen defense, but their excessive formation during sepsis can cause further inflammation and tissue damage. In sepsis, extracellular cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern, is released to induce NET formation.

An engineered poly(A) tail attenuates gut ischemia/reperfusion-induced acute lung injury.

Background: Gut ischemia/reperfusion causes the release of damage-associated molecular patterns, leading to acute lung injury and high mortality. Cold-inducible ribonucleic acid-binding protein is a ribonucleic acid chaperon that binds the polyadenylation tail of messenger ribonucleic acid intracellularly. Upon cell stress, cold-inducible ribonucleic acid-binding protein is released, and extracellular cold-inducible ribonucleic acid-binding protein acts as a damage-associated molecular pattern, worsening inflammation.