Distribution of the Tissue Plasminogen Activator (t‐pa) Promotor to Perivascular Sympathetic Nerves and Other Neural Crest Derivatives: Evidence of a Dispersed Plasmin Proteolysis

The recently shown release of a serine protease, t-PA, from sympathetic axon terminals into vascular smooth muscle marks an interesting new development in vascular biology1. This is due to the potential of released t-PA to activate plasmin and its multiple proteolytic effects within the vessel wall extracellular matrix. These fine, 0.5–2.0 micron filaments have long escaped notice in t-PA immunolocalizations. To better visualize them we created a transgenic mouse, to be described, in which the t-PA promoter - an indicator of the capacity to synthesize t-PA - and the green fluorescent protein are specifically targeted to neural crest-derived cells, including the sympathetic nervous system. Our initial images localized the promoter expression to the nerve plexus of several vessels, most strongly the densely innervated arterioles2. Newer images, to be shown, now visualize discrete positive expressions confined to other crest derivatives; eg adrenal chromaffin cells, melanocytes, Schwann cells; lymph node, thymus and spleen microvessels; corneal endothelium, iris, retinal ganglion cells and optic nerve. This dispersion suggests the existence of an extensive non endothelial, neural crest-derived system allowing released t-PA and plasmin proteolysis to permeate the interstitium of multiple tissues.