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Leukocyte-endothelial interactions and organ injury: the role of adhesion molecules
G A Talbott1, S R Sharar, J M Harlan
1Department of Anesthesiology, University of Washington School of Medicine, Seattle 98104.
Abstract:
Polymorphonuclear neutrophils (PMN) play an important role in host defense and immune surveillance. However, PMNs can be detrimental when inflammatory stimuli are excessive and can lead to uncontrolled PMN adherence to microvascular endothelium, resulting in tissue and organ injury in the critically ill. The molecular basis of PMN-endothelial adherence is dependent on two groups of adhesion molecules and their co-specific ligands: the beta 2 integrins and their counterstructures, which are members of the immunoglobulin gene superfamily; and the selectins and their carbohydrate ligands expressed on vascular mucins and other glycoproteins or glycolipids. This review characterizes the events leading to PMN-endothelial adhesion and examines a number of in vivo models in which adhesion molecule blockade has protected against injury. The role of adhesion molecules in T-lymphocyte adhesion and immune surveillance of transplant allografts is also briefly discussed. The infectious risks of adhesion molecule blockade are reviewed.
Insights
Polymorphonuclear neutrophils (PMNs) are crucial for host defense but can cause injury during severe inflammation. Understanding PMN-endothelial adherence via adhesion molecules is key to preventing tissue damage and exploring therapeutic blockade.
Area of Science:
- Immunology
- Cell Biology
- Vascular Biology
Background:
- Polymorphonuclear neutrophils (PMNs) are vital for host defense but can cause significant tissue injury during excessive inflammation.
- Uncontrolled PMN adherence to the microvascular endothelium is a key mechanism in critical illness-related organ damage.
- PMN-endothelial interactions are mediated by specific adhesion molecules, including beta 2 integrins and selectins.
Purpose of the Study:
- To review the molecular mechanisms underlying PMN-endothelial cell adherence.
- To examine in vivo models demonstrating the protective effects of adhesion molecule blockade against injury.
- To briefly discuss the role of adhesion molecules in T-lymphocyte function and transplant rejection, and review associated infectious risks.
Main Methods:
- Literature review focusing on the molecular basis of PMN-endothelial adherence.
- Analysis of in vivo experimental models investigating adhesion molecule blockade.
- Examination of studies on T-lymphocyte adhesion and infectious risks of therapeutic blockade.
Main Results:
- PMN-endothelial adherence involves beta 2 integrins and selectin families interacting with their ligands.
- Adhesion molecule blockade has shown protective effects against tissue and organ injury in various in vivo models.
- Adhesion molecules also influence T-lymphocyte adhesion, immune surveillance of allografts, and carry potential infectious risks.
Conclusions:
- Adhesion molecules are critical regulators of PMN-endothelial interactions, impacting inflammatory injury.
- Targeting adhesion molecules offers a potential therapeutic strategy for inflammatory conditions, with demonstrated efficacy in preclinical models.
- Further research is warranted to balance the benefits of adhesion molecule blockade against potential infectious risks and effects on immune surveillance.