In vitro adherence of lymphocytes to dermal endothelium under shear stress: implications in pathobiology and steroid therapy of acute cutaneous GVHD

摘要: The extravasation of leukocytes at sites inflammation critically depends on initial shear-resistant adhesive interactions between in blood flow and target tissue endothelium. Dermal lymphocytic infiltrates are a hallmark feature acute cutaneous graft-versus-host disease (acGVHD) following allogeneic hematopoietic stem cell (allo-HSC) transplantation. These occur commonly during periods profound lymphopenia, suggesting that the dermal endothelial mechanism(s) promoting lymphocyte emigration acGVHD highly efficient. To examine this issue, we performed Stamper-Woodruff assays frozen sections biopsy specimens lesions occurring within 100 days HSC transplantation 22 autologous transplant (auto-HSCT) 25 allo-HSCT recipients. By using shear-based assay, observed adherence to papillary vascular structures all punch recipients who had clinicohistologic evidence were not receiving steroids, whereas no was skin from did develop acGVHD. Within group auto-HSCT recipients, 2 biopsies demonstrated binding vessels. Among patients steroid therapy for acGVHD, endothelium abrogated prior resolution rash those responded, yet persistent one patient whose respond therapy. Collectively, these data indicate displays heightened capacity support adhesion under shear stress conditions suggest down-modulation capability may be mechanism by which steroids abrogate reactions.