P- and L-selectin mediate binding of T cells to chronically inflamed human airway endothelium

Eur J Immunol. 1999 Apr;29(4):1324-33. doi: 10.1002/(SICI)1521-4141(199904)29:04<1324::AID-IMMU1324>3.0.CO;2-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Chronic Disease
  • Endothelium / immunology
  • Humans
  • Integrins / physiology
  • L-Selectin / physiology*
  • Leukocyte Common Antigens / analysis
  • Membrane Glycoproteins / physiology
  • Nasal Mucosa / immunology*
  • Nasal Polyps / immunology*
  • P-Selectin / physiology*
  • Receptors, Lymphocyte Homing / physiology
  • T-Lymphocytes / physiology*

Substances

  • Integrins
  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Receptors, Lymphocyte Homing
  • L-Selectin
  • Leukocyte Common Antigens