Integrin Associated Protein‐CD47 regulates LFA‐1 and VLA‐4 integrins during leukocyte recruitment

Abstract

Recruitment of effector T-cells into tissues is regulated by molecular interactions of T-cells with the vascular endothelium. CD47 (Integrin Associated Protein) is broadly expressed and participates in leukocyte recruitment and in immune functions. CD47 functionally associates multiple integrins including αvβ3 and α4β1 (VLA-4). We examined if CD47 regulation of leukocyte LFA-1 and α4β1 integrins is required in T-cell recruitment. In a dermal air pouch model of TNF-α induced inflammation, CD47ko mice have an >80% reduction in T-cell, neutrophil and monocyte recruitment vs. WT mice at 4 and 24 hrs. Bone marrow (BM) transplantation of CD47ko mice with WT BM did not fully restore leukocyte recruitment to the air pouch, implicating contributions by both leukocytes and endothelial cells (EC). We next investigated leukocyte-EC adhesion in vitro with Th1 cells or endothelium from WT and CD47ko mice. The absence of CD47 on EC or Th1 cells reduced adhesion and transmigration, corroborating the air pouch data. T-cells and EC from CD47ko mice express similar levels of integrins and adhesion molecules, respectively, compared to WT. CD47ko Th1 cells, but not WT Th1 cells, showed reduced adhesion to immobilized ICAM-1/SDF-1 or VCAM-1 under flow conditions and normal adhesion to E-selectin. These results suggest CD47 is necessary for stimulus-induced VLA-4 and LFA-1 dependent adhesion and migration. Supported by NIH HL-36028.