ADHESION MOLECULE EXPRESSION ON PHAGOCYTIC MICROGLIAL CELLS FOLLOWINGANTEROGRADE DEGENERATION OF PERFORANT PATH AXONS

Entorhinal cortex lesion (ECL) leads to anterograde degeneration of pe rforant path axons and is known to induce a rapid and intense reaction of astrocytes and microglial cells in the deafferented dentate gyrus. Phagocytosis of degenerating axons involves the establishment and mai ntenance of cell-matrix and cell-cell interactions by activated glial cells. It was thus our aim to investigate whether the process of axon phagocytosis is accompanied by the expression of adhesion molecules on activated microglial cells or reactive astrocytes, as such molecules mediate both cell-matrix and cell-cell interactions. We found that the integrin adhesion molecules leukocyte function antigen-1 (LFA-1), ver y late antigen-4 (VLA-4), and the ligand for LFA-1, intercellular adhe sion molecule-1 (ICAM-1), were expressed on microglial cells accumulat ing in the outer molecular layer of the deafferented dentate gyrus. Th is upregulation of adhesion molecule expression on microglial cells sh owing morphological criteria of activation occurred rapidly following ECL, reached its peak at 3 days post lesion (dpl), and gradually retur ned to control levels after 9 dpl. Astrocytes were never labeled by an tibodies directed against these adhesion molecules. Prelabeling of the perforant path with a fluorescent tracer and subsequent ECL led to ph agocytosis of fluorescent-labeled axonal debris by cells that were loc ated in the outer molecular layer and showed typical microglial morpho logy. Double-fluorescence labeling demonstrated that microglial cells engaged in the phagocytosis of axonal debris expressed LFA-1, VLA-4, a nd the LFA-l-ligand ICAM-1. In conclusion, our results demonstrate tha t anterograde degeneration of perforant path axons results in adhesion molecule expression on activated microglial cells engaged in axon pha gocytosis. The expression of such molecules could represent a mechanis m that retains activated microglia in areas of axonal degeneration and perhaps enables the interaction of microglial cells with each other o r with other immunocompetent cells. (C) 1997 Wiley-Liss, Inc.