Red cell and endothelial Lu/BCAM beyond sickle cell disease.

Area of Science:

• Hematology
• Molecular Biology
• Cell Biology

Background:

• Blood group antigens, like Lutheran (Lu), have emerging roles beyond transfusion medicine.
• Lu/BCAM glycoproteins are identified as erythroid receptors mediating red blood cell adhesion to endothelium.
• Epinephrine stimulates Lu/BCAM-mediated cell adhesion to laminin, dependent on protein kinase A phosphorylation.

Purpose of the Study:

• To investigate the role of Lu/BCAM constitutive phosphorylation in abnormal red blood cell adhesion in polycythemia vera.
• To explore the in vivo function of Lu/BCAM glycoproteins in non-erythroid tissues.

Main Methods:

• Analysis of Lu/BCAM phosphorylation in polycythemia vera patients.
• Gene invalidation of Lu/BCAM in mice.
• Histological examination of kidney glomeruli and intestinal tissues in mutant mice.

Main Results:

• Constitutive Lu/BCAM phosphorylation is linked to abnormal red blood cell adhesion in polycythemia vera, suggesting a role in thrombosis.
• Lu/BCAM glycoproteins are crucial for maintaining basement membrane organization in non-erythroid tissues.
• Lu/BCAM-deficient mice show glomerular basement membrane thickening and intestinal smooth muscle disorganization.

Conclusions:

• Lu/BCAM plays a significant role in both physiological and pathological cell adhesion.
• Minor blood group antigens like Lu/BCAM have critical functions in erythroid and non-erythroid tissues.
• Understanding Lu/BCAM function provides insights into polycythemia vera pathogenesis and basement membrane biology.