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Related Experiment Videos

Orchestrated information transfer underlying leukocyte endothelial interactions

K Ebnet1, E P Kaldjian, A O Anderson

  • 1Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.

Annual Review of Immunology
|January 1, 1996
PubMed
Summary

This study explores how immune cells, called leukocytes, communicate with endothelial cells lining blood vessels. The process involves a multi-step adhesion cascade that allows leukocytes to rapidly interpret signals from endothelial cells. The first step, primary adhesion, involves molecules like selectins and integrins and depends on the density of receptors on leukocyte microvilli. Chemokines, which are signaling molecules, are presented by endothelial cells either directly or by relaying signals from nearby tissue. Endothelial cells follow specific rules for signal transduction, including redundancy and synergy. Soluble mediators reach endothelial cells via diffusion for short distances and fiber bundles for longer distances. The findings suggest that leukocyte-endothelial interactions are highly coordinated and efficient.

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Area of Science:

  • Immunology and inflammation signaling
  • Cell adhesion and vascular biology
  • Signal transduction in immune responses

Background:

Leukocyte migration to sites of inflammation involves complex communication between immune cells and endothelial cells. Prior research has shown that leukocytes bind to endothelial cells through a multi-step adhesion cascade. However, the exact mechanisms by which information is transferred from tissue to endothelium and then to leukocytes remain unclear. While it was already known that selectins and integrins mediate initial adhesion, the role of chemokines and the rules governing their signaling remain uncertain. This gap motivated investigations into how leukocytes interpret endothelial signals and how endothelial cells translate tissue-derived information into leukocyte-targeted signals. No prior work had resolved how soluble mediators reach endothelial cells over long distances. The uncertainty around these mechanisms drove the need for a comprehensive analysis of information transfer in leukocyte-endothelial interactions.

Purpose Of The Study:

Keywords:
leukocyte adhesion mechanismsendothelial cell signalingimmune cell traffickingchemokine function in inflammation

Frequently Asked Questions

The multi-step adhesion cascade involves primary adhesion (rolling/tethering), triggering, and strong adhesion. It allows leukocytes to rapidly interpret endothelial signals.

Yes, integrins contribute to primary adhesion alongside selectins and depend on receptor concentration on leukocyte microvilli.

Chemokines reach endothelial cells either through direct posting or by relaying signals from tissue-derived information.

Endothelial signal transduction follows principles of specificity, redundancy, amplification, and synergy.

Related Experiment Videos

The study aimed to clarify how leukocytes interpret endothelial signals and how endothelial cells translate tissue-derived information into leukocyte-targeted signals. The researchers focused on three key information-transfer points: leukocyte reading of endothelial information, endothelial transformation of tissue-derived signals into leukocyte signals, and the delivery of soluble mediators to endothelial cells. They sought to determine whether the multi-step adhesion cascade is a universal mechanism across leukocyte types. The study also aimed to explore whether chemokines serve as primary signals in triggering adhesion and whether endothelial cells use redundancy and synergy to amplify signals. The researchers wanted to assess if fiber bundles facilitate long-range transport of soluble mediators. This work sought to address unresolved questions about the specificity and efficiency of leukocyte-endothelial communication.

Main Methods:

The researchers reviewed existing literature to identify patterns in leukocyte-endothelial interactions. They analyzed the adhesion cascade involving primary adhesion, triggering, and strong adhesion. The study examined how chemokines are presented by endothelial cells either through direct posting or by relaying signals from tissue. The researchers evaluated the role of integrins and receptor concentration on leukocyte microvilli in primary adhesion. They also assessed the rules governing endothelial signal transduction, including specificity, redundancy, amplification, and synergy. The study considered how soluble mediators reach endothelial cells, distinguishing between simple diffusion and fiber-assisted transport. The researchers used a synthesis approach to integrate findings across T cells, monocytes, and eosinophils. The analysis focused on the mechanisms rather than experimental validation.

Main Results:

The multi-step adhesion cascade is a general mechanism for leukocyte binding, involving primary adhesion, triggering, and strong adhesion. Primary adhesion is mediated not only by selectins but also by integrins and depends on receptor concentration on leukocyte microvilli. Chemokines are presented by endothelial cells either through direct posting or by relaying signals from tissue-derived information. Endothelial signal transduction follows principles of specificity, redundancy, amplification, and synergy. The endothelium integrates multiple signals and produces chemokines and adhesion molecules in a coordinated manner. Soluble mediators reach endothelial cells via simple diffusion for short distances. Longer-range transport is facilitated by fiber bundles, especially those surrounded by fibroblastic reticular cells in lymph nodes. The study confirmed the universality of the adhesion cascade across T cells, monocytes, and eosinophils. These findings suggest that the system is optimized for rapid and efficient information transfer.

Conclusions:

The study concludes that leukocyte-endothelial interactions rely on a multi-step adhesion cascade optimized for rapid information readout. The adhesion process involves primary adhesion, triggering, and strong adhesion, with integrins and receptor concentration playing a role in primary adhesion. Chemokines are presented by endothelial cells either through direct posting or by relaying signals from tissue-derived information. Endothelial cells follow specific rules for signal transduction, including redundancy, amplification, and synergy. Soluble mediators reach endothelial cells via diffusion for short distances and fiber bundles for longer distances. The findings suggest that the system is highly coordinated and efficient. The study supports the generality of the adhesion cascade across multiple leukocyte types. The conclusions align with the authors' statements about the mechanisms of information transfer in leukocyte-endothelial interactions.

Long-range transport of soluble mediators is facilitated by fiber bundles, especially in lymph nodes.

The study confirms the adhesion cascade is a general mechanism for T cells, monocytes, and eosinophils.