Abstract
Inflammatory caspase sensing of cytosolic lipopolysaccharide (LPS) triggers pyroptosis and the concurrent release of damage-associated molecular patterns (DAMPs). Collectively, DAMPs are key determinants that shape the aftermath of inflammatory cell death. However, the identity and function of the individual DAMPs released are poorly defined. Our proteomics study revealed that cytosolic LPS sensing triggered the release of galectin-1, a β-galactoside-binding lectin. Galectin-1 release is a common feature of inflammatory cell death, including necroptosis. In vivo studies using galectin-1-deficient mice, recombinant galectin-1 and galectin-1-neutralizing antibody showed that galectin-1 promotes inflammation and plays a detrimental role in LPS-induced lethality. Mechanistically, galectin-1 inhibition of CD45 (Ptprc) underlies its unfavorable role in endotoxin shock. Finally, we found increased galectin-1 in sera from human patients with sepsis. Overall, we uncovered galectin-1 as a bona fide DAMP released as a consequence of cytosolic LPS sensing, identifying a new outcome of inflammatory cell death.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Alarmins / deficiency
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Alarmins / genetics
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Alarmins / metabolism*
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Animals
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Case-Control Studies
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Disease Models, Animal
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Endotoxemia / chemically induced
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Endotoxemia / immunology*
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Endotoxemia / metabolism
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Endotoxemia / pathology
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Female
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Galectin 1 / blood
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Galectin 1 / deficiency
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Galectin 1 / genetics
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Galectin 1 / metabolism*
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HeLa Cells
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Humans
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Inflammation / chemically induced
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Inflammation / immunology*
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Inflammation / metabolism
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Inflammation / pathology
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Inflammation Mediators / metabolism*
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Intracellular Signaling Peptides and Proteins / deficiency
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Leukocyte Common Antigens / metabolism
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Lipopolysaccharides
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Macrophages / immunology
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Macrophages / metabolism*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Middle Aged
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Necroptosis
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Phosphate-Binding Proteins / deficiency
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Phosphate-Binding Proteins / genetics
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Phosphate-Binding Proteins / metabolism*
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RAW 264.7 Cells
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Sepsis / blood
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Sepsis / diagnosis
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Signal Transduction
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Up-Regulation
Substances
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Alarmins
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Galectin 1
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Gsdmd protein, mouse
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Inflammation Mediators
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Intracellular Signaling Peptides and Proteins
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LGALS1 protein, human
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Lgals1 protein, mouse
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Lipopolysaccharides
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Phosphate-Binding Proteins
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Leukocyte Common Antigens
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Ptprc protein, mouse