P- and L-selectin mediate binding of T cells to chronically inflamed human airway endothelium.
The inflammatory process that underlies allergic diseases such as asthma is characterized by tissue infiltration of eosinophils and T cells. We have used the Stamper-Woodruff frozen-section assay to characterize the receptors involved in adhesion of human peripheral blood T cells to nasal polyp endothelium (NPE) as a model of T cell migration in allergic disease. T cells bound specifically to NPE in a temperature-, cell concentration- and shear stress-dependent fashion. Adhesion was inhibited by approximately 70% by antibodies against P-selectin and its counter-receptor P-selectin glycoprotein-1 (PSGL-1). In addition, a blocking monoclonal antibody (mAb) against L-selectin caused significant although lesser inhibition. Cells adhering to NPE were primarily of the CD45RO+ memory subset. Although only a minority subset of peripheral blood T cells expressed functional PSGL-1, as determined by binding of a P-selectin Fc chimera, the majority of the P-selectin chimera-binding cells were found to be CD45RO+. This is consistent with the observation that memory T cells bind to NPE via P-selectin. Using blocking mAb we also investigated which integrins and their counter-structures were involved in T cell binding. A combination of anti-beta1 and beta2 mAb was able to inhibit adhesion by almost 50%. An antibody against intercellular adhesion molecule (ICAM)-2 gave an inhibition similar to that by anti-CD18 mAb, suggesting ICAM-2 was the major counter-receptor involved for the beta2 integrin component. This study suggests that P-selectin, and to a lesser extent L-selectin, may be acting as specific homing receptors for the airway mucosa in the context of chronic allergic disease.
Symon
F A
FA
Division of Respiratory Medicine, Leicester University Medical School, Glenfield Hospital, GB.
McNulty
C A
CA
Wardlaw
A J
AJ
D002448:Cell Adhesion; D002908:Chronic Disease; D004727:Endothelium / Q000276:immunology; D006801:Humans; D016023:Integrins / Q000502:physiology; D019041:L-Selectin / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008562:Membrane Glycoproteins / Q000502:physiology; D009297:Nasal Mucosa / Q000276:immunology*; D009298:Nasal Polyps / Q000276:immunology*; D019007:P-Selectin / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*
D016023:Integrins; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin; D017493:Leukocyte Common Antigens