SERP-1 Mechanism of Action

Initial studies with Serp-1 used immunohistochemical analysis of tissue specimens from animal models of cellular invasion at early times after injury. In the rat and rabbit models there was a consistent early reduction in the invasion of macroplu and nonspecific CD2-positive, nonspecific lymphocyte (specifically NK cell) invasion from 24 hours up to 72 hours after Serp-1 treatment post angioplasty injury or aortic, cardiac and renal transplant. Similar reductions in macrophage cells and CD2-positive lymphocytes were detected at early follow-up after acute cardiac ( 48 hours) and chronic renal transplant models. This reduction was greater than the eflfrcts of Serp-1 alone or cyclosporine treatment alone in these same models. This reduction in inflammatory cell invasion correlated closely with later reductions in plaque growth and r sculopathy development. 

It should be noted that many viral proteins exhibit more than one frmetion, often targeting two or more host response pathways. Serp-1 targets tPA, uPA, plasmin in the thrombolytic cascade and also foctor in the thrombotic cascade which represent more than one receptor and signaling pathway. It is certainly possible that this h hly potent viral serpin may have acquired other 

Viral Serpins That Target Apoptotic Pathways Preclinical Analysis ofCRMAandSERP-2 

Spi-1 is a less well described rabbit poxvirus intracellular protein with circumscribed anti-apoptotic activity. This viral serpin binds cathepsin G similar to the reports for the mammalian intracellular PI-6 protein. Spi-1 has been reported to inhibit a caspase independent form of apoptosis in selected cells.  

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