International Journal of Inflammation, Cancer and Integrative Therapy
Open Access

Plasminogen; Plasmin; Inflammation resolution; Immune cells; Cytokines; Tissue repair; crosstalk; Inflammatory mediators; Therapeutic implications

Introduction

Inflammation is a fundamental biological response essential for defending the body against various threats, including pathogens and tissue damage. While inflammation serves as a protective mechanism, its uncontrolled or prolonged activation can contribute to tissue damage and chronic diseases [4]. The process of inflammation resolution is a precisely orchestrated sequence of events aimed at restoring tissue integrity and function. Recent research has highlighted the intricate interplay between the plasminogen/plasmin system and inflammation resolution, unveiling a previously underappreciated dimension of their functional relationship.

The plasminogen/plasmin system, initially recognized for its role in fibrinolysis and tissue remodeling, has emerged as a multifaceted player in various physiological processes. Plasminogen, synthesized primarily by the liver, can be activated to its enzymatic form, plasmin, by plasminogen activators such as tPA and uPA. Beyond its traditional role in clot dissolution, plasmin has been implicated in immune cell modulation, extracellular matrix remodeling, and inflammation resolution [5 ].

Inflammation resolution entails the coordinated withdrawal of immune cells from the inflammatory site, restoration of tissue architecture, and attenuation of pro-inflammatory signals. This process is not merely the cessation of the inflammatory response but an active and dynamic sequence of events driven by specific molecular interactions [6 ]. Plasmin's involvement in inflammation resolution has been demonstrated through its impact on immune cell recruitment, clearance of apoptotic cells, and regulation of cytokine signaling.

The interplay between the plasminogen/plasmin system and inflammation resolution is characterized by bidirectional communication. Inflammatory mediators can influence the expression and activation of plasminogen activators, thereby modulating plasmin production. Conversely, plasmin-generated fragments can interact with immune cells, cytokines, and chemokines, influencing their activity and function. Achieving a balance between pro-inflammatory and anti-inflammatory effects of the plasminogen/plasmin system is pivotal for effective inflammation resolution [7].

As our understanding of the molecular intricacies of inflammation resolution and the plasminogen/plasmin system deepens, new opportunities for therapeutic intervention arise. Dysregulation of either system can lead to chronic inflammatory disorders, tissue fibrosis, and impaired wound healing. By targeting specific components of these systems, researchers aim to develop innovative therapeutic strategies for managing inflammatory diseases and promoting tissue repair [8]. Through further investigation, the potential to harness the synergistic effects of the plasminogen/plasmin system and inflammation resolution holds promise for improved clinical outcomes in a variety of inflammatory conditions.

Plasminogen/plasmin system

Plasminogen, a zymogen synthesized by the liver, can be activated to its active form, plasmin, by various proteases, including tissuetype plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Plasmin is known for its role in degrading fibrin clots and extracellular matrix components. However, recent research has shown that plasmin also interacts with immune cells, cytokines, and other molecules involved in inflammation resolution [9].

Interactions with immune cells

Plasmin plays a role in modulating immune cell recruitment and activation during inflammation resolution. Plasmin-generated fragments, such as angiostatin and kringle domains, exhibit antiinflammatory properties by inhibiting leukocyte adhesion and migration. Plasmin can also cleave cell surface receptors, affecting immune cell signaling and function [10 ].

Resolution of inflammation

Inflammation resolution is an active process involving the removal of immune cells, the restoration of tissue architecture, and the suppression of pro-inflammatory signals. Plasmin contributes to these processes by promoting the clearance of apoptotic neutrophils, a critical step in inflammation resolution. Plasmin-mediated degradation of extracellular matrix components can facilitate tissue remodeling and repair.

Crosstalk between systems

The interaction between the plasminogen/plasmin system and inflammation resolution is bidirectional. Inflammatory mediators, such as cytokines and chemokines, can influence the expression and activation of plasminogen activators. Conversely, plasmin-generated fragments can modulate immune cell responses and cytokine production [11]. The balance between pro-inflammatory and antiinflammatory effects of the plasminogen/plasmin system is essential for proper inflammation resolution.

Clinical implications

Understanding the crosstalk between the plasminogen/ plasmin system and inflammation resolution has significant clinical implications. Dysregulation of either system can lead to chronic inflammatory conditions, tissue fibrosis, or impaired wound healing. Targeting specific components of these systems may offer novel therapeutic strategies for managing inflammatory diseases [12].

Conclusion

The intricate interplay between the plasminogen/plasmin system and inflammation resolution highlights their cooperative roles in maintaining tissue homeostasis. This cross-regulation involves immune cell interactions, cytokine modulation, and tissue remodeling. Further research is needed to unravel the specific molecular mechanisms underlying this crosstalk and to develop targeted therapeutic approaches to harness the anti-inflammatory potential of the plasminogen/plasmin system.

Acknowledgement

None

Conflict of Interest

None

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