Orchestrated Information Transfer Underlying Leukocyte Endothelial Interactions

Abstract

The specificity and efficiency of leukocyte binding to endothelial cells (ECs) depends on coordinated information transfer from the underlying tissue to endothelium and from there to the leukocyte. We address three distinct information-transfer points in this system: 1. How does the leukocyte read information from the EC? This process is best accounted for by the paradigm of a multi-step adhesion cascade optimized for rapid information readout; it consists of primary adhesion (rolling/tethering), triggering, and strong adhesion. Recent studies with T cells, monocytes, and eosinophils confirm the generality of the paradigm. The concept of primary adhesion has been expanded to involve not only the selectins, but also certain integrins; furthermore, it depends on receptor concentration on leukocyte microvilli. 2. What information from the underlying tissue does the EC transform into signals for the leukocytes? And what rules govern that process? We illustrate the principles with chemokines, believed to participate in the triggering step. The endothelium displays chemokines either (a) directly by “posting” them from other cells or (b) by integrating a variety of tissue and environmental signals and “relaying” that information by producing its own chemokines and surface adhesion molecules. The rules for this endothelial transduction include specificity coupled with redundancy, amplification, synergy, and coordinated induction of ensembles of molecules. Finally, 3. How does the relevant information reach the endothelium? Simple diffusion is sufficient to deliver signals from cells close to the vessel. However, longer range soluble mediator transport appears to be facilitated by fiber bundles, particularly those ensheathed by fibroblastic reticular cells in the lymph node.