Plasma gelsolin (pGSN)

Quick links:
-> Proposed Mechanism of Action
-> General Gelsolin Information
-> Gelsolin Binding
-> pGSN Levels in Disease
-> Tissue Effects of pGSN Repletion
-> Survival Effects of pGSN Repletion

Proposed Mechanism of Action of Plasma Gelsolin (pGSN)

Plasma gelsolin (pGSN) appears to be a key component in the innate system in animals that is the critical, non-specific mechanism that localizes inflammation to the actual site of injury and prevents the initiation of inappropriate, dysregulated systemic inflammation.

As such, catastrophic drops in pGSN levels resulting from severe tissue injury in either acute or chronic illness leave the body at risk for exaggerated systemic inflammatory responses to local injury. This vulnerability can be identified by measuring pGSN levels which, if abnormally low, usually precede the actual systemic inflammatory mediator “storm” and the resulting signs of dysregulated inflammatory cascades by hours to months.

Increasingly, epidemiological evidence has linked systemic pGSN depletion with poor outcome not only in critical illness but also in a variety of sub-acute and chronic diseases.

In acute illness, the proposed mechanism of action of circulating pGSN in localizing inflammation is graphically shown as follows. In the vast majority of cases, local pGSN depletion is minor after tissue insult thus allowing the remaining circulating pGSN to prevent inflammatory mediators from initiating an inappropriate systemic inflammatory response. Occasionally, however, with severe local depletion, the overall depletion of the circulating pGSN is such that there are insufficient reserves of pGSN to “buffer” the onslaught of released inflammatory mediators resulting in catastrophic general activation of the numerous cytokine cascades. In acute injuries, this can manifest as the development of multiple organ system failure, often leading to death. In more chronic conditions systemic hyper-inflammatory states can lead to a heightened susceptibility to dying from infection and, probably, accelerated atherosclerosis. Restoration of circulating pGSN to levels above the critical threshold may restore the natural control of systemic inflammation and prevent or suppress the onset of such complications.

As suggested in the diagram above, repletion of pGSN with recombinant human pGSN (rhu-pGSN, Solinex™) after the inciting incident but before any clinical signs or symptoms of sepsis syndrome can ameliorate the outcome of the insult in several animal models of acute disease.