Integrin-Mediated Inflammation in Anesthetic Contexts
Summary
Integrins are transmembrane heterodimers that orchestrate cell adhesion, migration and innate immune responses. In the perioperative setting, volatile and intravenous anaesthetic agents modulate integrin-mediated signalling, thereby influencing leukocyte–endothelial interactions, cytokine release and pathogen clearance. This interplay has profound implications for infection risk, organ protection and postoperative recovery. Central to anaesthetic modulation is the regulation of β2 integrins such as Mac-1 and LFA-1, which govern neutrophil and monocyte recruitment via ligand-specific binding and downstream pathways. Emerging evidence highlights that anaesthetics can exert ligand-specific blockade, alter small GTPase activity and affect integrin affinity states, balancing host defence against pathological inflammation. Understanding these mechanisms may guide tailored anaesthetic strategies that minimise complications and exploit protective immunomodulation.
Research from Nature Portfolio
Recent studies have elucidated a ligand-targeted approach to modulate integrin function without compromising host defence. A novel monoclonal antibody against Mac-1’s pro-inflammatory ligand interaction has been shown to selectively inhibit leukocyte recruitment while preserving phagocytic activity, reducing cytokine storms and diminishing mortality in sepsis models. This targeted blockade preserves alternative ligand interactions, offering a refined anti-inflammatory strategy that avoids broad immunosuppression and supports the development of integrin-specific therapeutics in perioperative care.
Integrin-Mediated Inflammation in Anesthetic Contexts publication trend
The graph below shows the total number of articles in integrin-mediated inflammation in anesthetic contexts across all publications each year (not limited to Nature Index journals).
Technical terms
Integrin: A transmembrane receptor mediating cell–cell and cell–extracellular matrix adhesion, crucial for leukocyte trafficking and activation.
Mac-1 (CD11b/CD18): A β2 integrin on monocytes and neutrophils that binds pro-inflammatory ligands, directing leukocyte recruitment and phagocytosis.
LFA-1 (CD11a/CD18): A β2 integrin on lymphocytes and leukocytes essential for firm adhesion to endothelium and immunological synapse formation.
Rap1: A small GTPase regulating inside-out signalling of integrins, controlling adhesion and cytoskeletal dynamics.
Ligand-specific blockade: A therapeutic strategy targeting a single integrin–ligand interaction while sparing other integrin functions.
References
- A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense. Nature Communications (2018).
- Volatile anesthetics affect macrophage phagocytosis. PLOS ONE (2019).
- Stereoselectivity of Isoflurane in Adhesion Molecule Leukocyte Function-Associated Antigen-1. PLOS ONE (2014).
- Comparison between sevoflurane and propofol on immunomodulation in an in vitro model of sepsis. Frontiers in Medicine (2023).
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