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Infection and Immunity, October 1998, p. 5001-5007, Vol. 66, No. 10
Department of Molecular Microbiology and Immunology, Oregon
Health Sciences University, Portland, Oregon
97201-30981;
Division of Radiation
Biology, CBRL, Department of Radiation Oncology, Stanford University,
Stanford, California 943052; and
Glycobiology Program, The Burnham Institute, La Jolla Cancer
Research Center, La Jolla, California 920373
Received 1 April 1998/Returned for modification 11 May
1998/Accepted 29 June 1998
Members of our group reported recently that neisseria infection of
human epithelial cells results in accelerated degradation of the major
lysosomal integral membrane protein LAMP1 and that this is due to
hydrolysis of this glycoprotein at its immunoglobulin A1 (IgA1)-like
hinge by the neisseria type 2 IgA1 protease (L. Lin et al., Mol.
Microbiol. 24:1083-1094, 1997). We also reported that the IgA1
protease plays a major role in the ability of the pathogenic neisseriae
to survive within epithelial cells and hypothesized that this is due to
alteration of lysosomes as a result of protease-mediated LAMP1
degradation. In this study, we tested the hypothesis that neisseria
infection leads to multiple changes in lysosomes. Here, we report that
neisseria infection also reduces the levels of three other lysosomal
markers: LAMP2, lysosomal acid phosphatase (LAP), and CD63. In
contrast, neither the epidermal growth factor receptor level nor the
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Infection of Epithelial Cells by Pathogenic
Neisseriae Reduces the Levels of Multiple Lysosomal
Constituents
-tubulin level is affected. A detailed examination of LAMP2
indicated that the reduced LAMP2 levels are not the result of an
altered biosynthetic rate or of cleavage by the IgA1 protease.
Nevertheless, the protease plays a role in reducing LAMP2 and LAP
activity levels, as these are partially restored in cells infected with
an iga mutant. We conclude that neisseria infection results
in multiple changes to the lysosomes of infected epithelial cells and
that these changes are likely an indirect result of IgA1
protease-mediated cleavage of LAMP1.
*
Corresponding author. Mailing address: Department of
Molecular Microbiology and Immunology, Oregon Health Sciences
University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201-3098. Phone: (503) 494-7768. Fax: (503) 494-6862. E-mail:
somaggie{at}ohsu.edu.
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