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

Abstract

Objective. To assess the laminins in basement membrane of the labial salivary glands of patients with Sjögren's syndrome (SS) and healthy controls.Methods. Labeling of laminin ␣1-␣5, ␤1, ␤2, ␥1, and ␥2 chains was performed using immunohistochemistry with chain-specific monoclonal antibodies and pattern recognition analysis of the labeled specimens.Results. Laminin ␣1, ␣2, and ␣4 chains were detected exclusively in the acinar basement membranes, whereas laminin ␣3, ␣5, ␤1, ␥1, and ␥2 chains were also detected in ductal basement membranes. Laminin ␤2 chain was not found. In patients with SS, laminin ␣1 and ␣2 chains were weakly labeled, but laminin ␣4 labeling was also intense in areas not infiltrated by lymphocytes. Pattern recognition analysis suggested that laminin ␣1, ␣2, and ␣4 chains were associated with acinar cells, myoepithelial cells, and tissue damage/ repair, respectively.Conclusion. 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 ␣1 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 ␣1 chain/laminin 1 in acinar basement membrane and its weak expression in SS with acinar cell atrophy. The impairment of myoepithelial laminin ␣2 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.

Sex steroids in Sjögren’s syndrome

“…With the help of the combinatorial rules of the LM a, b and g chains it could be concluded that the corresponding laminins were LM-111 (earlier laminin-1), LM-211 (earlier laminin-2) and LM-411 (earlier laminin-8). Interestingly, in SS LM-111 and LM-211 staining of the acinar basement membrane was very weak [26]. There was some apparent controversy about LM-111 levels, which however has been resolved [28].…”

“…Characterization of basement membrane laminins [26] and collagen type IV a-chains [27] disclosed that in healthy salivary glands three laminin a-chains were only found in the acinar basement membrane, but not in the ductal basement membrane. These laminin a-chains were LM-a1, LM-a2 and LM-a4 chains.…”

Primary Sjögren’s Syndrome: Current Pathophysiological, Diagnostic and Therapeutic Advances

“…In normal salivary glands, laminin 5 bridges the basal lamina with epithelial cells by forming adhesion complexes through specific integrin 64 (Velozo et al, 2009). Modified expression of basal laminins, laminins 1 and 5, occurs during different stages of SS (Kwon et al, 2006;Laine et al, 2004). In salivary acinar cells from SS patients, altered distribution of 64 integrin results in the destruction epithelial cell complexes with laminins (Velozo et al, 2009).…”

Alterations in type I hemidesmosome components suggestive of epigenetic control in the salivary glands of patients with Sjögren's syndrome

“…In addition, LSG samples from patients with SS display reduced immunodetection of laminins 111 and 211, which is paralleled by an increase in laminin 411 at locations distant from inflammatory foci (3). However, protein levels of laminins 111 and 332 were augmented, indicating that remodeling of the BL occurred (2).…”

“…Severe alterations in acinar cells and the extracellular matrix (ECM) are recurrent observations in the labial salivary glands (LSGs) of patients with primary Sjögren's syndrome (SS) (1)(2)(3)(4). LSG epithelial cells are linked to the basal lamina (BL) through several transmembrane protein complexes that have important functions in adhesion and cell signaling (5).…”