Negative impact of recipient SPRED2 deficiency on transplanted lung in a mouse model

Area of Science:

• Transplantation immunology
• Organ injury mechanisms
• Molecular signaling pathways

Background:

• Ischemia-reperfusion injury (IRI) is a major cause of primary graft dysfunction following lung transplantation.
• The Sprouty-related EVH1-domain-containing (SPRED) protein family, including SPRED2, negatively regulates the mitogen activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathway.

Purpose of the Study:

• To investigate the role of SPRED2 in lung IRI following orthotopic lung transplantation in a mouse model.
• To elucidate the impact of SPRED2 deficiency on IRI severity and associated molecular signaling.

Main Methods:

• Orthotopic syngeneic lung transplantation was performed in wild-type and Spred2 knockout mice.
• Post-reperfusion assessment included arterial oxygen tension measurements and histological evaluation using a Lung Injury Score.
• Intragraft analysis of ERK1/2 activation and expression of proinflammatory cytokines/chemokines.

Main Results:

• Spred2 knockout recipients exhibited significantly more severe lung IRI compared to wild-type recipients.
• Histological analysis revealed exacerbated airway epithelial damage, interstitial edema, hemorrhage, and neutrophil infiltration in Spred2 knockout grafts.
• Increased intragraft ERK1/2 activation and elevated levels of proinflammatory cytokines and chemokines were observed in Spred2 knockout recipients.

Conclusions:

• SPRED2 plays a critical protective role against lung IRI in the context of lung transplantation.
• Targeting the MAPK/ERK pathway in transplantation recipients may represent a potential therapeutic strategy for preventing lung IRI.