Segment‐specific but pathologic laminin isoform profiles in human labial salivary glands of patients with Sjögren's syndrome

Abstract

To assess the laminins in basement membrane of the labial salivary glands of patients with Sjogren's syndrome (SS) and healthy controls. Labeling of laminin alpha1-alpha5, beta1, beta2, gamma1, and gamma2 chains was performed using immunohistochemistry with chain-specific monoclonal antibodies and pattern recognition analysis of the labeled specimens. Laminin alpha1, alpha2, and alpha4 chains were detected exclusively in the acinar basement membranes, whereas laminin alpha3, alpha5, beta1, gamma1, and gamma2 chains were also detected in ductal basement membranes. Laminin beta2 chain was not found. In patients with SS, laminin alpha1 and alpha2 chains were weakly labeled, but laminin alpha4 labeling was also intense in areas not infiltrated by lymphocytes. Pattern recognition analysis suggested that laminin alpha1, alpha2, and alpha4 chains were associated with acinar cells, myoepithelial cells, and tissue damage/repair, respectively. All salivary gland basement membranes signal through laminin 5, laminin 6, and laminin 10 trimers, but acinar basement membranes also signal through laminin 1, laminin 2, and laminin 8 trimers. Laminin alpha1 chain/laminin 1 may play a central role in the maintenance of acinar cells in healthy glands. This possibility was supported by the finding of variable expression of laminin alpha1 chain/laminin 1 in acinar basement membrane and its weak expression in SS with acinar cell atrophy. The impairment of myoepithelial laminin alpha2 chain/laminin 2 in patients with SS indicates a double defect in the acinar compartment and pathologic extracellular matrix-to-cell signaling, which may contribute to structural deterioration and functional abnormality of the exocrine glands.