Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

Abstract

Gelsolin, an actin-depolymerizing protein expressed both in extracellular fluids and in the cytoplasm of a majority of human cells, has been recently implicated in a variety of both physiological and pathological processes. Its extracellular isoform, called plasma gelsolin (pGSN), is present in blood, cerebrospinal fluid, milk, urine, and other extracellular fluids. This isoform has been recognized as a potential biomarker of inflammatory-associated medical conditions, allowing for the prediction of illness severity, recovery, efficacy of treatment, and clinical outcome. A compelling number of animal studies also demonstrate a broad spectrum of beneficial effects mediated by gelsolin, suggesting therapeutic utility for extracellular recombinant gelsolin. In the review, we summarize the current data related to the potential of pGSN as an inflammatory predictor and therapeutic target, discuss gelsolin-mediated mechanisms of action, and highlight recent progress in the clinical use of pGSN.

Recombinant Human Plasma Gelsolin Stimulates Phagocytosis while Diminishing Excessive Inflammatory Responses in Mice with Pseudomonas aeruginosa Sepsis

“…Sepsis and septic shock represent very serious medical conditions that require a complex therapeutic approach and use of a spectrum of drugs assuring multidirectional biological activity. A compelling number of studies report that pGSN, apart from having actin-scavenging properties, exerts a number of effects in pathogenesis including protection against infections, implication in wound healing and re-epithelization, bone remodeling, and the stabilization of intracellular calcium concentrations [5,22]. Importantly, in mice not expressing GSN, dysfunction in inflammatory reactions, including the delayed in vivo migration of neutrophils and impaired chemotaxis was observed [23].…”

“…Recently, pGSN was recognized as a key factor modulating host immune responses due to the preferential binding of microbial-derived endotoxins, resulting in prevention of toll-like receptor (TLR) activation [3,4]. A compelling number of studies also recognize plasma gelsolin as a potential biomarker of inflammation [5][6][7][8][9][10][11].…”

“…It is suggested that repletion with exogenous recombinant pGSN might preempt, limit, or reverse the negative effects of hypogelsolinemia [5]. The pleotropic actions of pGSN supplementation could improve the host antimicrobial defense by different mechanisms, including the improvement of bacterial clearance by macrophages via nitric oxide synthase 3 (NOS3)-dependent mechanisms and restoring bacterial binding and uptake by murine and human macrophages, impaired during acute tissue injuries [4,12].…”

Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

“…We report substantially decreased (~2.6x) levels of gelsolin (GSN) (Figure 4b,c). Plasma gelsolin is a part of the extracellular actin scavenger system (EASS), which removes toxic F-actin filaments that have been released from necrotic cells to the bloodstream (Piktel et al, 2018) . Low levels of plasma gelsolin are associated with inflammation: it is believed that gelsolin is recruited to the sites of tissue injury to handle the released actin, depleting its plasma levels.…”

Metabolomic and Proteomic Stratification of Equine Osteoarthritis

“…Gelsolin (82-84 kDa) is a multifunctional, calcium ion-regulated actin filament severing, capping, and nucleating protein which is involved in the determination of cell shape, secretion and chemotaxis (83,84). Previous studies of gelsolin on different biological systems have identified gelsolin as a potential predictor of both inflammation and tissue injury (85)(86)(87). Within rheumatoid arthritis patients, reduced circulating levels of plasma gelsolin have been identified (88).…”