Severe alterations in expression and localisation of alpha 6 beta 4 integrin in salivary gland acini from patients with Sjogren syndrome

Abstract

Objectives: In salivary glands from patients with Sjogren syndrome, overexpression of laminins 1 and 5 and disorganisation 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 alpha 6 beta 4 integrin. In the present work, mRNA and protein levels of alpha 6 beta 4 integrin were determined and its localisation in salivary glands. Methods: Salivary glands of 12 patients with Sjogren syndrome and 8 controls were studied. The mRNA and protein levels of alpha 6 beta 4 were determined by semiquantitative reverse transcriptase (RT)-PCR and western blot analysis, respectively. The subcellular localisation of alpha 6 beta 4 and laminin were evaluated by confocal microscopy. Results: In patients, no significant differences in alpha 6 and beta 4 mRNA levels were detected. However, beta 4 integrin protein levels were significantly lower, whereas, changes in alpha 6, were highly variable. In controls, alpha 6 beta 4 was detected in the basolateral and basal surface of serous and mucous acini, respectively. In patients, alterations in alpha 6 beta 4 distribution were particularly dramatic for acini with strong basal lamina disorganisation. alpha 6 beta 4 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 alpha 6 beta 4 integrin and the formation of new cell-cell adhesions that help maintain acinar organisation and promote cell survival. Conversely, in cases with severe basal lamina alterations, lateral alpha 6 beta 4 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.

Objectives: In salivary glands from patients with Sjogren syndrome, overexpression of laminins 1 and 5 and disorganisation 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 alpha 6 beta 4 integrin. In the present work, mRNA and protein levels of alpha 6 beta 4 integrin were determined and its localisation in salivary glands. Methods: Salivary glands of 12 patients with Sjogren syndrome and 8 controls were studied. The mRNA and protein levels of alpha 6 beta 4 were determined by semiquantitative reverse transcriptase (RT)-PCR and western blot analysis, respectively. The subcellular localisation of alpha 6 beta 4 and laminin were evaluated by confocal microscopy. Results: In patients, no significant differences in alpha 6 and beta 4 mRNA levels were detected. However, beta 4 integrin protein levels were significantly lower, whereas, changes in alpha 6, were highly variable. In controls, alpha 6 beta 4 was detected in the basolateral and basal surface of serous and mucous acini, respectively. In patients, alterations in alpha 6 beta 4 distribution were particularly dramatic for acini with strong basal lamina disorganisation. alpha 6 beta 4 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 alpha 6 beta 4 integrin and the formation of new cell-cell adhesions that help maintain acinar organisation and promote cell survival. Conversely, in cases with severe basal lamina alterations, lateral alpha 6 beta 4 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.