Expression of endothelial cell adhesion molecules in human bronchial xenografts.
The role of endothelial cell adhesion molecules (CAMs) in the selective recruitment of leukocyte subsets to the airway remains unclear. The goal of the present study was to examine the expression of human endothelial CAM in a cytokine-induced airway inflammatory response. To accomplish this, an in vivo model of human bronchus was developed by heterotopically transplanting intact sections of human airway into severe combined immunodeficient (SCID) mice. Three weeks after transplantation, the xenografts closely resembled normal bronchus with little evidence of rejection. Less than 15% of the submucosal vessels expressed E-selectin and vascular cell adhesion molecule-1 (VCAM-1), whereas intercellular adhesion molecule-1 (ICAM-1) was present constitutively on approximately 35% of bronchial microvessels. Intrabronchial instillation of tumor necrosis factor-alpha (TNF-alpha) significantly increased expression of microvascular E-selectin to 40%, ICAM-1 to 65%, and VCAM-1 to 41%, and was accompanied by an influx of murine leukocytes into the bronchial submucosa. These results demonstrate that the human bronchial microvasculature expresses cytokine-inducible adhesion molecules. Mast cells and other resident or migratory cells that secrete TNF-alpha may thus activate the bronchial microvasculature and thereby recruit leukocytes to the airway.
Pilewski
J M
JM
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
Panettieri
R A
RA
Kaiser
L R
LR
Albelda
S M
SM
D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000187:drug effects / Q000378:metabolism*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation*; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D019040:E-Selectin; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D051379:Mice; D016513:Mice, SCID; D009504:Neutrophils / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1
D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1