Role of LFA-1/ICAM-1, CLA/E-selectin and VLA-4/VCAM-1 pathways in recruiting leukocytes to the various regions of the chronic leg ulcer

Abstract

The center, edge and distant regions of the venous leg ulcer differ in inflammatory cell composition, suggesting that these represent different developmental stages. Our goal was to determine which recruitment pathways contribute to the differences in leukocyte composition between the various ulcer regions. The multiple region biopsy approach, which enables to study the different development phases of the ulcer at one time-point, was employed to immunohistochemically identify the vascular adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and their counter-ligands on extravasated leukocyte cutaneous lymphocyte-associated antigen (CLA), lymphocyte function-associated antigen (LFA-1) and very late activation antigen-4 (VLA-4), respectively. E-selectin expression was highest at the ulcer edge, while ICAM-1 was highest at the ulcer center. VCAM-1 expression was minor at all ulcer regions. CLA stained up to 80% of the epidermal Langerhans' cells, 62% of the T cells, and only 9% of the macrophages. LFA-1 did not stain Langerhans' cells, stained up to 89% of the T cells and up to 11% of the macrophages. VLA-4 stained up to 30% of the T cells and 71% of the macrophages. In conclusion, the results indicate that Langerhans' cells, T cells and macrophage are each recruited by more than one adhesion-molecule pathway to any of the chronic venous leg ulcer regions.