RESEARCH - Severe alterations in expression and localization of 64 integrin in salivary gland acini from Sjogren's syndrome patients

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Ann Rheum Dis. Published Online First: 14 July 2008. doi:10.1136/ard.2008.089607

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Extended Report

Severe alterations in expression and localization of 64 integrin in

salivary gland acini from Sjögren's syndrome patients

José Velozo 1, Aguilera 2, Cecilia Alliende 1, Ewert

1, Claudio Molina 3, Paola Pérez 1, Lisette Leyton 1, Quest 1,

Mónica Brito 1, González 1, Cecilia Leyton 1, Marcela Hermoso

1, Romo 4 and María-ta González 1*

1 Institute of Biomedical Sciences, Faculty of Medicine, University of

Chile, Chile

2 INDISA Clinic, Chile

3 Mayor University, Chile

4 Santa María Clinic, Chile

Abstract

Objectives: In salivary glands from Sjögren's syndrome patients,

overexpression of laminin-1 and -5 and disorganization of the acinar

basal lamina have been reported. Laminin-5 mediates association of the

basal lamina with epithelial cells by forming adhesion complexes upon

interaction with 6 & beta]4 integrin. Here, we determine mRNA and

protein levels of 64 integrin and evaluate its localization in

salivary glands from Sjögren's syndrome patients.

Methods: Salivary glands of 12 Sjögren's syndrome patients and 8

controls were studied. The mRNA and protein levels of 64 were

determined by semiquantitative RT-PCR and Western blot analysis,

respectively. The subcellular localization of 64 and laminin were

evaluated by confocal microscopy.

Results: In patients, no significant differences in 6 and 4 mRNA

levels were detected. However, 4 integrin protein levels were

significantly lower, whereas, changes in 6, were highly variable. In

controls, 64 was detected in the basolateral and basal surface of

serous and mucous acini, respectively. In patients, alterations in 64

distribution were particularly dramatic for acini with strong basal

lamina disorganization. 64 was also detected in the cytoplasm and

lateral plasma membrane in serous and mucous acini.

Conclusion: Mild alterations in the basal lamina correlated with

lateral redistribution of 64 integrin, and the formation of new

cell-cell adhesions that help maintain acinar organization and promote

cell survival. Conversely, in cases with severe basal lamina

alterations, lateral 64 redistribution was no longer sufficient to

maintain acinar cell survival. Thus, maintenance of equilibrium

between cell-cell and cell-basal lamina attachment is required to

sustain gland cell survival.

http://ard.bmj.com/cgi/content/abstract/ard.2008.089607v1?papetoc

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