Tissue plasminogen activator and neuroserpin are widely expressed in the human central nervous system

Tambet Teesalu; Andres Kulla; Aadu Simisker; Vappu Sirén; Daniel A. Lawrence; Toomas Asser; Antti Vaheri

doi:10.1160/TH02-12-0310

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(02): 358-368
DOI: 10.1160/TH02-12-0310

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Tissue plasminogen activator and neuroserpin are widely expressed in the human central nervous system

Authors

Tambet Teesalu

¹Haartman Institute, University of Helsinki and HUCH Laboratory Diagnostics, Finland

³Department of Neurology and Neurosurgery, University of Tartu, Estonia

⁴Applied Phenomics LLC,Tartu, Estonia
Andres Kulla

²Department of Pathology and Neuropathology, University of Tartu, Estonia
Aadu Simisker

²Department of Pathology and Neuropathology, University of Tartu, Estonia
Vappu Sirén

¹Haartman Institute, University of Helsinki and HUCH Laboratory Diagnostics, Finland
Daniel A. Lawrence

⁵Department of Vascular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland, USA
Toomas Asser

³Department of Neurology and Neurosurgery, University of Tartu, Estonia
Antti Vaheri

¹Haartman Institute, University of Helsinki and HUCH Laboratory Diagnostics, Finland

Abstract

Summary

Tissue plasminogen activator (tPA) is increasingly recognized to play important roles in various physiological and pathological processes in the central nervous system (CNS). Much of the data on the involvement of plasminogen activators in neurophysiology and -pathology have been derived from studies on experimental animals. We have now performed a systematic characterization of the expression of tPA and its inhibitor, neuroserpin, in normal human CNS. Brain and spinal cord samples from 30-36 anatomic locations covering all major brain regions were collected at 9 autopsies of donors with no neurological disease. Tissues were embedded in paraffin and tissue arrays were constructed. In two cases parallel samples were snap-frozen for biochemical analysis. Expression and activity profiling of tPA and neuroserpin were performed by immunohistochemistry, in situ hybridization, immunocapture and zymography assays. In the adult CNS, tPA was expressed at the mRNA and protein levels in many types of neurons, in particular in thalamus, cortex of cerebellum, pontine nuclei, neocortex, limbic system, and medulla oblongata. Interestingly, tPA was often co-expressed with its CNS inhibitor, neuroserpin. Despite overlapping expression of tPA and neuroserpin, zymography and immunocapture assays demonstrated that human neural tissue is a rich source of active tPA. Our analysis documents a detailed map of expression of tPA and its inhibitor in the human CNS and is compatible with the view that tPA is a key player in CNS physiology and pathology.

Keywords

Tissue plasminogen activator - neuroserpin - human central nervous system - neuron - tissue array

Full Text

References

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