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Blockade of CXCR2 signalling: a potential therapeutic target for preventing neutrophil-mediated inflammatory diseases
Nithin B Boppana1, Asokan Devarajan, Kaliappan Gopal
1Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA.
Abstract:
Polymorphonuclear neutrophils (PMN) play a key role in host innate immune responses by migrating to the sites of inflammation. Furthermore, PMN recruitment also plays a significant role in the pathophysiology of a plethora of inflammatory disorders such as chronic obstructive pulmonary disease (COPD), gram negative sepsis, inflammatory bowel disease (IBD), lung injury, and arthritis. Of note, chemokine-dependent signalling is implicated in the amplification of immune responses by virtue of its role in PMN chemotaxis in most of the inflammatory diseases. It has been clinically established that impediment of PMN recruitment ameliorates disease severity and provides relief in majority of other immune-associated disorders. This review focuses on different novel approaches clinically proven to be effective in blocking chemokine signalling associated with PMN recruitment that includes CXCR2 antagonists, chemokine analogs, anti-CXCR2 monoclonal antibodies, and CXCR2 knock-out models. It also highlights the significance of the utility of nanoparticles in drugs used for blocking migration of PMN to the sites of inflammation.
Insights
Blocking neutrophil migration via chemokine signaling offers therapeutic potential for inflammatory diseases like COPD and arthritis. Novel approaches, including CXCR2 antagonists and nanoparticles, are explored to impede polymorphonuclear neutrophil (PMN) recruitment.
Area of Science:
- Immunology
- Pharmacology
- Nanotechnology
Background:
- Polymorphonuclear neutrophils (PMN) are crucial in innate immunity and inflammation.
- PMN recruitment drives inflammatory diseases like COPD, sepsis, IBD, lung injury, and arthritis.
- Chemokine signaling amplifies immune responses by directing PMN chemotaxis.
Purpose of the Study:
- To review novel strategies for blocking chemokine signaling in PMN recruitment.
- To highlight therapeutic approaches targeting PMN migration in inflammatory conditions.
Main Methods:
- Review of clinically proven methods to block chemokine signaling.
- Analysis of CXCR2 antagonists, chemokine analogs, and anti-CXCR2 monoclonal antibodies.
- Examination of CXCR2 knock-out models and nanoparticle drug delivery systems.
Main Results:
- Several novel approaches effectively block chemokine signaling and PMN recruitment.
- Targeting CXCR2 demonstrates significant therapeutic potential.
- Nanoparticles show promise for enhancing drug delivery in blocking PMN migration.
Conclusions:
- Inhibiting PMN recruitment ameliorates inflammatory disease severity.
- Novel CXCR2-targeting agents and nanoparticle-based therapies represent promising strategies for inflammatory disorders.
- Further research into these approaches could lead to improved treatments for a range of immune-associated conditions.
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