Abstract
Membrane-type matrix metalloprotease (MT-MMP) is an activator of gelatinase A (MMP-2), which has previously been found in carcinoma cells. We examined non-neurological and Alzheimer's disease brain tissues for MT-MMP by immunohistochemistry and in situ hybridization. The anti-MT-MMP antibodies gave positive staining of brain microglial cells in all the brain tissues. Positively stained microglia were found only in the white matter. The cells producing MT-MMP protein were also shown to be white matter microglia. These results provide further evidence that activated gelatinase A, which may be a processing enzyme for degradation of β-amyloid protein, may be produced in white matter microglia.
References
Bernstein H-G, Bruszis S, Schmidt D, Wiederanders B, Dorn A (1989) Immunodetection of cathepsin D in neuritic plaques found in brains of patients with dementia of Alzheimer type. J Hirnforsch 30:613–618
Bernstein H-G, Kirschke H, Wiederanders B, Schmidt D, Rinne A (1990) Antigenic expression of cathepsin B in aged human brain. Brain Res Bull 24:543–549
Cataldo AM, Thayer CY, Bird ED, Wheelock TR, Nixon RA (1990) Lysosomal proteinase antigens are prominently localized within senile plaques of Alzheimer's disease: evidence for a neuronal origin. Brain Res 513:181–192
Khachaturian ZS (1985) Diagnosis of Alzheimer's disease. Arch Neurol 42:1097–1105
Kojima SI, Omori M (1992) Two-way cleavage of beta-amyloid protein precursor by multicatalytic proteinases. FEBS Lett 304:57–60
Ladror US, Snyder SW, Wang GT, Holzman TF, Kraft GA (1994) Cleavage at the amino and carboxyl termini of Alzheimer's amyloid-β by cathepsin D. J Biol Chem 269:18422–18428
McDermott JR, Gibson AM (1991) The processing of Alzheimer A4 β-amyloid protein precursor: identification of a human brain metallopeptidase which cleaves-Lys-Leu-in a model peptide. Biochem Biophys Res Commun 179:1148–1154
McGeer PL, Akiyama H, Kawamata T, Yamada T, Walker DG, Ishii T (1992) Immunohistochemical localization of betaamyloid precursor protein sequences in Alzheimer and normal brain tissue by light and electron microscopy. J Neurosci Res 31:428–442
Miyazaki K, Hasegawa M, Funahashi K, Umeda M (1993) A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor. Nature 362:839–841
Sapirstein VS, Durrie R, Berg MJ, Marks N (1994) Amyloid precursor protein is enriched in axolemma and periaxolemmalmyelin and associated clathrin-coated vesicles. J Neurosci Res 37:348–358
Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, Seiki M (1994) A matrix metalloporotease expressed on the surface of invasive tumor cells. Nature 370:61–65
Siman R, Card JP, Davis LG (1990) Proteolytic processing of β-amyloid precursor by calpain I. J Neurosci 10:2400–2411
Tokuda T, Tanaka K, Kametani F, Ikeda S, Yanagisawa N (1994) Secretory form of β-amyloid precursor protein is much abundantly contained in the cerebral white matter in human brain. Neurosci Lett 175:33–36
Welgus HG, Fliszar CJ, Seltzer JL, Schmid TM, Jeffrey JJ (1990) Differential susceptibility of type X collagen to cleavage by two mammalian interstitial collagenases and 72-kDa type IV collagenase. J Biol Chem 265:13521–13527
Yamada T, Miyazaki K, Koshikawa N, Takahashi M, Akatsu H, Yamamoto T (1995) Selective localization of gelatinase A, an enzyme degrading β-amyloid protein, in white matter microglia and in Schwann cells. Acta Neuropathol 89:199–203
Zhong Z, Higaki J, Murakami K, Wang Y, Catalano R, Quon D, Cordell B (1994) Secretion of β-amyloid precursor protein involves multiple cleavage sites. J Biol Chem 269:627–632
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Yamada, T., Yoshiyama, Y., Sato, H. et al. White matter microglia produce membrane-type matrix metalloprotease, an activator of gelatinase A, in human brain tissues. Acta Neuropathol 90, 421–424 (1995). https://doi.org/10.1007/BF00294800
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DOI: https://doi.org/10.1007/BF00294800