Table 1.

Properties of plasmin(ogen) in inflammation and immunity.

Target Effects	Properties of Plasmin(ogen)	References
Proinflammatory Macrophage and Monocyte effects	Interacts with macrophage migration and activation via plasminogen receptors. Promotes cytokine production in macrophages.	[32,35,62]
	Directly alters gene expression in macrophages by binding plasminogen receptors and enhancing phagocytic capacity, efferocytosis and foam cell formation.	[37,63,64]
	Promote macrophage phagocytosis in mice	[36]
	Potent chemoattractant of monocytes, induces actin polymerisation.	[65]
	Activates 5-lipoxygenase pathway in monocytes and macrophages resulting in the synthesis of proinflammatory leukotrienes.	[66]
	Stimulates JAK/STAT signalling in monocytes resulting in MCP-1 release, further promoting monocyte recruitment.	[67]
	Increases phagocytic activity of DCs without causing activation.	[38]
Dendritic Cell (DC) effects	This interaction is involved in the chemoattraction of dendritic cells, T- and B cells. Triggers chemotaxis of monocyte derived DCs and a T helper type-1 (Th1) phenotype in CD4+ T cells.	[68]
	Indirectly promotes neutrophil recruitment by binding to mast cells and stimulating release of leukotrienes	[69]
	Induce expression of CCR6-activating chemokine CCL20 in dermis via induction of NF-kB.	[70]
Other inflammatory effects	Stimulates NF-kB and AP-1, resulting in the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, and tissue factor.	[71]
	Activates phospholipase A2 in endothelial cells, releasing arachidonic acid and subsequent production of prostacyclin, enhanced nitric oxide (NO)-mediated vasorelaxation and chemotactic monocyte chemotactic protein (MCP)-1 release.	[39,72,73]
	In pulmonary epithelial cells, plasmin induces cyclooxygenase (COX)-2, resulting in the release of antifibrotic prostaglandin E-2 (PGE-2).	[74]
	Promotes complement activation.	[17,75]
	Binds to platelets via PAR-4 and dose-dependently activate or inhibit platelet activation and aggregation. Interacts with extracellular matrix, endothelial cells, smooth muscle.	[76,77]
	Plasmin can activate the Matrix Metalloproteinases, transforming growth factor (TGF)-β, and neurotrophic factors.	[78,79,80]
	Inhibition of DC maturation following phagocytosis thereby inducing a tolerogenic phenotype. Reduced migration of DCs to lymph nodes and increase release of TGF-β. Reduction in DC ability to induce allogeneic lymphocyte proliferation.	[38]
Immuno-suppression DC effects	Suppression of proinflammatory cytokines in vivo, reversed by tranexamic acid. Inhibition of plasmin reduces post-surgical infection rates.	[33]