Galectin-3 Mediates Heme-Induced Multi-Organ Dysfunction by Modulating the Splenic Immune Microenvironment.

Area of Science:

• Immunology
• Hematology
• Pathology

Background:

• Acute intravascular hemolysis releases heme, causing systemic inflammation and organ damage.
• Galectin-3 (Gal-3) is an inflammatory modulator, but its role in heme-induced injury is unclear.

Purpose of the Study:

• To investigate the role of Gal-3 in heme-induced organ injury.
• To determine how Gal-3 influences the immune response during hemolysis.

Main Methods:

• A phenylhydrazine (PHZ)-induced acute hemolysis model in wild-type (WT) and Gal-3 knockout (KO) mice.
• Assessment of tissue damage, hemolysis levels, anemia, and splenic immune cell populations.

Main Results:

• Gal-3 deficiency reduced liver, kidney, and pancreas injury despite similar hemolysis levels.
• WT mice showed a pro-inflammatory splenic environment with Gal-3.
• Gal-3 KO mice exhibited an immunoregulatory phenotype with increased regulatory T cells and IL-10+ macrophages, preserving organ architecture.

Conclusions:

• Gal-3 mediates heme-induced systemic inflammation and organ injury.
• Absence of Gal-3 promotes an immunoregulatory splenic phenotype, alleviating multi-organ stress.
• Gal-3 is a potential therapeutic target for managing complications in acute hemolytic crises.