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Infection and Immunity, October 1998, p. 5001-5007, Vol. 66, No. 10
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

Patricia Ayala,1 Lan Lin,2 Sylvia Hopper,1 Minoru Fukuda,3 and Magdalene So1,*

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 beta -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.


Infection and Immunity, October 1998, p. 5001-5007, Vol. 66, No. 10
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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