Plasmin: A Modulator of Immune Function

Draxler, Dominik F.; Sashindranath, Maithili; Medcalf, Robert L.

doi:10.1055/s-0036-1586227

Cited by 79 publications

(91 citation statements)

References 112 publications

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“…Essentially, upon calcium and/or thrombin addition, PRP forms a platelet-rich fibrin scaffold (PRF) that can be layered in the wound bed. PRF degradation is highly regulated by the serine protease system from plasma PAI-1, PAI-2 (plasminogen activator inhibitor type 1 and 2), TAF1 (TATA-box binding protein, associated factor), plasmin [12,13] and can be synchronized with the healing process.…”

Section: Introductionmentioning

confidence: 99%

Wound Dressing Selection Is Critical to Enhance Platelet-Rich Fibrin Activities in Wound Care

Amo

Perez‐Valle

Pérez-Zabala

et al. 2020

IJMS

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The use of platelet-rich fibrin (PRF) is investigated in ulcer management because it provides a healing milieu rich in growth factors and cytokines. Although crucial, the relevance of secondary dressings is under-researched and no data support the use of any particular dressing in preference to another. We assessed the properties of different dressing categories, including alginates, hydrocolloids, foams, hydrofibers, films, meshes and gauzes, in terms of affinity for PRF, releasate management (retention/extrusion) and the kinetics of cytokine release as well as the influence of each combination product, [PRF + dressing], on dermal cell behaviour, aiming to provide useful information for choosing the most adequate dressing for each particular patient. Active dressings including alginates, hydrofibers, foams and hydrocolloids blend with PRF, creating a diverse combination of products with different performances. Alginate and hydrofiber showed the highest affinity but moderate retention of releasate, without interfering with cell functions. Instead, the foam sequestered the releasate and hindered the release of growth factors, thereby compromising cell activities. Film and mesh presented very poor releasate retention and performed similarly to PRF by itself. Affinity index and releasate management explained 79% of platelet-derived growth factor (PDGF-BB) concentration variability, p < 0.001. Cell proliferation depended on the ability of the combination product to retain/release supernatant, PDGF-BB concentration and cell adhesion R 2 = 0.91, p = 0.014.

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Section: Introductionmentioning

confidence: 99%

Wound Dressing Selection Is Critical to Enhance Platelet-Rich Fibrin Activities in Wound Care

Amo

Perez‐Valle

Pérez-Zabala

et al. 2020

IJMS

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“…We have recently reviewed the complex implications of plasmin as a modulator of the immune response. 8 We propose that plasmin is differentially regulating the inflammatory and the innate immune response after TBI: plasmin boosts the local inflammatory response to tissue injury by enhancing leukocyte recruitment and phagocytic activity, thereby promoting the clearance of dead cell material and tissue repair. On the other hand, plasmin prevents the migration of antigen presenting cells to secondary lymphatic organs (such as the cLN) (illustrated schematically in Figure 7).…”

Section: Discussionmentioning

confidence: 99%

“…Plasmin therefore has become recognized for its broader involvement in physiological and pathophysiological processes, which is at least in part mediated by various plasminogen receptors on leukocytes and tissue bound cells . Plasmin can also modulate the immune system on several levels . It has been implicated in inflammatory processes by direct interaction with proinflammatory and anti‐inflammatory mediators as well as various leukocyte subsets, by binding to cell‐surface plasminogen receptors and inducing intracellular signaling .…”

Section: Introductionmentioning

confidence: 99%

“…7 Plasmin can also modulate the immune system on several levels. 8 It has been implicated in inflammatory processes by direct interaction with proinflammatory and anti-inflammatory mediators as well as various leukocyte subsets, by binding to cell-surface plasminogen receptors and inducing intracellular signaling. 9 In contrast, monocyte-derived dendritic cells treated with plasmin exhibit enhanced phagocytic capacity, yet a reduced ability to migrate to the draining lymph nodes and to mount an allogeneic immune response.…”

Section: Introductionmentioning

confidence: 99%

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Tranexamic acid modulates the cellular immune profile after traumatic brain injury in mice without hyperfibrinolysis

Draxler

Daglas

Fernando

et al. 2019

Journal of Thrombosis and Haemostasis

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Background Traumatic brain injury (TBI) is known to promote immunosuppression, making patients more susceptible to infection, yet potentially exerting protective effects by inhibiting central nervous system (CNS) reactivity. Plasmin, the effector protease of the fibrinolytic system, is now recognized for its involvement in modulating immune function. Objective To evaluate the effects of plasmin and tranexamic acid (TXA) on the immune response in wild‐type and plasminogen‐deficient (plg−/−) mice subjected to TBI. Methods Leukocyte subsets in lymph nodes and the brain in mice post TBI were evaluated by flow cytometry and in blood with a hemocytometer. Immune responsiveness to CNS antigens was determined by Enzyme‐linked Immunosorbent Spot (ELISpot) assay. Fibrinolysis was determined by thromboelastography and measuring D‐dimer and plasmin‐antiplasmin complex levels. Results Plg−/− mice, but not plg+/+ mice displayed increases in both the number and activation of various antigen‐presenting cells and T cells in the cLN 1 week post TBI. Wild‐type mice treated with TXA also displayed increased cellularity of the cLN 1 week post TBI together with increases in innate and adaptive immune cells. These changes occurred despite the absence of systemic hyperfibrinolysis or coagulopathy in this model of TBI. Importantly, neither plg deficiency nor TXA treatment enhanced the autoreactivity within the CNS. Conclusion In the absence of systemic hyperfibrinolysis, plasmin deficiency or blockade with TXA increases migration and proliferation of conventional dendritic cells (cDCs) and various antigen‐presenting cells and T cells in the draining cervical lymph node (cLN) post TBI. Tranexamic acid might also be clinically beneficial in modulating the inflammatory and immune response after TBI, but without promoting CNS autoreactivity.

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“…Draxler et al then further describe the role of plasmin as a modulator of the immune response and specifically address the role of plasmin in tissue homeostasis and the detrimental effects of dysregulated plasmin generation in chronic and acute inflammatory states. 8 The possibility that antifibrinolytic agents act also as antiinflammatory drugs is discussed. This additional function of antifibrinolytic agents may be relevant for patients with trauma or undergoing major surgery that receive antifibrinolytic drugs.…”

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confidence: 99%