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J. Exp. Med.,
Volume 187, Number 4, February 16, 1998 451-460
By
From the Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff,
CF4 4XX, United Kingdom
The brain is an immunoprivileged organ isolated from the peripheral immune system. However, it has been shown that resident cells, notably astrocytes and microglia, can express numerous innate immune molecules, providing the capacity to generate a local antipathogen system.
Perforin is a cytolytic protein present in the granules of cytotoxic T lymphocytes and natural
killer cells. Expression in cells other than those of the hemopoetic lineage has not been described. We report here that fetal astrocytes in culture (passages 2 to 15), astrocytoma, and adult
astrocytes expressed perforin. Reverse transcriptase polymerase chain reaction followed by
Southern blot was carried out using multiple specific primers and all cDNAs were cloned and
sequenced. Human fetal astrocyte perforin cDNA sequence was ~100% identical to the reported perforin cDNA cloned from T cells. Western blot analysis using monoclonal and polyclonal antiperforin peptide antibodies revealed a protein of 65 kD in both human fetal astrocyte
and rat natural killer cell lysates (n = 4). Immunostaining followed by FACS® and confocal and
electron microscopy analysis revealed that perforin was expressed by 40-50% of glial fibrillary
acidic protein positive cells present in the fetal brain culture (n = 11). Perforin was not localized to granules in astrocytes but was present throughout the cytoplasm, probably in association
with the endoplasmic reticulum. Perforin was not detected in normal adult brain tissue but was present in and around areas of inflammation (white and grey matter) in multiple sclerosis and
neurodegenerative brains. Perforin-positive cells were identified as reactive astrocytes. These
findings demonstrate that perforin expression is not unique to lymphoid cells and suggest that
perforin produced by a subpopulation of astrocytes plays a role in inflammation in the brain.
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