ASTROCYTE GROWTH, REACTIVITY, AND THE TARGET OF THE ANTIPROLIFERATIVEANTIBODY, TAPA

Reactive astrocytes form a scar alter injury to the CNS that many inve stigators believe contributes to the lack of functional regeneration. In the present study, Lye identify an astrocytic membrane protein that appears to play an important role in reactive gliosis and scar format ion, Cultures of rat astrocytes were used as a model system to produce and to screen monoclonal antibodies that would alter cell growth. One antibody, AMP1, was identified that depresses the mitotic activity of cultured glial cells and alters their morphology. Expression cloning reveals that the antigen on the external surface of the cultured glial cells has a high degree of homology with the human lymphocyte protein called Target of the Anti-Proliferative Antibody (TAPA-1; this rat pr otein will be referred to as rTAPA). rTAPA is a member of the tetramem brane-spanning superfamily of proteins and, as with other members of t his family of proteins, rTAPA is associated with the regulation of cel lular interactions and mitotic activity. After an injury to the cerebr al cortex, there is a dramatic increase in AMP1 immunoreactivity that is spatially restricted to the reactive astrocytes at the glial scar. This change represents an upregulation of a membrane protein, rTAPA, t hat is approximately equal to the increase observed for glial fibrilla ry acidic protein. The high levels of rTAPA at the site of CNS injury and the AMP1 antibody perturbation studies indicate that rTAPA may pla y a prominent role in the response of astrocytes to injury and in glia l scar formation.