Abnormal basement membrane type IV collagen alpha-chain composition in labial salivary glands in Sjögren's syndrome.

OBJECTIVE: Sjögren's syndrome (SS) is characterized by atrophy and malfunction of the acinar cells. The aim of this study was to investigate whether type IV collagen alpha-chain composition of acinar cell compartments could be abnormal in diseased glands. METHODS: Messenger RNA (mRNA) from human submandibular gland (HSG) cells, cultured with or without growth factor-depleted Matrigel, was analyzed using quantitative reverse transcription-polymerase chain reaction (RT-PCR). Labial salivary glands were analyzed using quantitative RT-PCR and immunohistochemistry. RESULTS: HSG cells of both the ductal and acinar phenotypes synthesized all alpha-chain mRNA, in particular those of the alpha1 and alpha2 chains. Labial salivary glands (LSGs) contained alpha1/2 chains but also contained mRNA of all the other alpha-chains, although the mRNA copy numbers for the alpha3 and alpha4 chains were low, and the corresponding proteins were absent. Type IV collagen alpha1/2-chains were observed in all tubuloalveolar basement membranes. In healthy glands, alpha5 and alpha6 chains were continuous around ducts but discontinuous around acini. In SS glands, these chains were absent or patchy around the ducts and absent around the acini. CONCLUSION: Ductal and acinar epithelial cells are able to locally produce mRNA for all 6 different alpha-chains. Type IV collagen alpha1/2-chains seem to form the backbone in the tubuloalveolar basement membrane in salivary glands. Type IV collagen alpha3 and alpha4 chain mRNA were found in cultured salivary epithelial cells and LSG explants but were not translated to the corresponding alpha-chains in LSGs. Both alpha5 and alpha6 mRNA were observed in salivary epithelial cells and glands. In healthy glands, immunolabeling always disclosed corresponding alpha-chains around ducts, but their synthesis and/or degradation seemed to be locally regulated around acinar cells. [ABSTRACT FROM AUTHOR]