E-selectin early overexpression induced by allogeneic activation in isolated mouse lung

Area of Science:

• Immunology
• Transplantation Biology
• Cellular and Molecular Medicine

Background:

• Host lymphocyte and graft endothelial cell interactions are crucial in graft rejection.
• Early endothelial cell activation is a critical event in transplant immunology.

Purpose of the Study:

• To investigate the kinetics of early endothelial cell activation following E-selectin engagement in a lung transplantation model.
• To elucidate the role of E-selectin in allogeneic lymphocyte adhesion and endothelial cell activation.

Main Methods:

• Utilized an isolated ventilated mouse lung model perfused with isogeneic or allogeneic blood.
• Employed real-time polymerase chain reaction, immunostaining, and enzyme-linked immunoadsorbent assay to analyze molecular changes.
• Investigated the involvement of the protein kinase C (PKC) pathway using specific inhibitors and antibodies.

Main Results:

• Isogeneic perfusion induced non-specific endothelial cell activation with upregulation of E-selectin, ICAM-1, TNF-alpha, IL-2, and lymphotoxin-alpha mRNA.
• Allogeneic perfusion led to loose lymphocyte adhesion mediated by E-selectin and endothelial expression of I-A molecule.
• E-selectin expression was confirmed to be independent of TNF-alpha triggering and involved the PKC pathway.

Conclusions:

• E-selectin upregulates its own expression and that of I-A, VCAM-1, TNF-alpha, and lymphotoxin-alpha mRNAs, while downregulating LFA-3 and ICAM-1 mRNAs.
• E-selectin significantly contributes to allogeneic lymphocyte adhesion and early endothelial cell activation in lung allografts.
• These early events mediated by E-selectin are implicated in structural and functional lung alterations post-transplantation.