acid-phosphatase and Sjogren-s-Syndrome

Sjögren's syndrome is a chronic autoimmune disease affecting the lacrimal glands and other epithelia. It has been suggested that acinar cells of the lacrimal glands provoke local autoimmune responses, leading to Sjögren's syndrome when they begin expressing major histocompatibility complex (MHC) class II molecules. We used isopycnic centrifugation and phase partitioning to resolve compartments that participate in traffic between the basolateral membranes and the endomembrane system to test the hypothesis that MHC class II molecules enter compartments that contain potential autoantigens, i.e., La/SSB, and enzymes capable of proteolytically processing autoantigen, i.e., cathepsins B and D. A series of compartments identified as secretory vesicle membranes, prelysosomes, and microdomains of the trans-Golgi network involved in traffic to the basolateral membrane, to the secretory vesicles, and to the prelysosomes were all prominent loci of MHC class II molecules, La/SSB, and cathepsins B and D. These observations support the thesis that lacrimal gland acinar cells that have been induced to express MHC class II molecules function as autoantigen processing and presenting cells.

Topics: Acid Phosphatase; alpha-Glucosidases; Animals; Antigen Presentation; Autoantigens; beta-N-Acetylhexosaminidases; Biological Transport; Cathepsin B; Cathepsin D; Cell Fractionation; Centrifugation, Density Gradient; Endothelium; Female; Galactosyltransferases; Histocompatibility Antigens Class II; Hydrogen-Ion Concentration; Immunoblotting; Lacrimal Apparatus; Membrane Proteins; rab GTP-Binding Proteins; Rabbits; Ribonucleoproteins; Sjogren's Syndrome; Sodium-Potassium-Exchanging ATPase; SS-B Antigen; Subcellular Fractions

The events that lead to Sjögren's autoimmune processes in the lacrimal gland remain poorly understood. The acinar cell's responses to acute cholinergic stimulation include release of secretory products across the apical plasma membrane (apm) and a number of processes related to traffic between endomembrane compartments and the basal-lateral plasma membranes (blm), such as recruitment of Na, K-ATPase, accelerated recycling, and accelerated transcytosis of secretory IgA. We tested the hypothesis that stimulation-induced acceleration of endomembrane traffic is accompanied by changes in compartmentation and increased blm expression of proteins that are normally sequestered in endomembrane compartments. Isolated rabbit lacrimal gland acinar cells were cultured in serum-free media for 2 days. After harvesting, cells were incubated with or without 10 microm carbachol at 37 degrees C for 20 min. Cells were lysed, and lysates were analysed by isopycnic centrifugation on sorbitol gradients. Galactosyltransferase catalytic activity was determined biochemically. Different forms of cathepsin B were detected by Western blotting. Carbachol stimulation decreased the contents of beta-hexosaminidase, alpha-glucosidase, and protein in secretory vesicles and increased them in specific compartments of the trans-Golgi network (ld-tgns). Stimulation also caused levels of galactosyltransferase, preprocathepsin B, and procathepsin B to increase two- to three-fold in the blm as well as increasing in the ld-tgns. Other changes caused by sustained stimulation included: (a) increased levels of protein and procathepsin B in compartments of the lysosomal pathway; (b) changes in the distributions of Rab5 within the endomembrane system; (c) changes in the distribution of Rab6 within the Golgi complex and tgn; (d) decreased expression of acid phosphatase and MHC class II molecules in the blm; and (e) decreased total content of Na,K-ATPase, which appeared to have been selectively depleted from the tgn and blmre. We propose that the normal compartmentation of certain proteins may allow them to remain cryptic, such that they are not subject to central tolerance. Stimulation-induced increases in the levels expressed at the blm or secreted to the interstitium may, therefore, contribute to initiation of local autoimmune responses.

Topics: Acid Phosphatase; alpha-Glucosidases; Animals; beta-N-Acetylhexosaminidases; Carbachol; Cathepsin B; Cathepsins; Cell Membrane; Cells, Cultured; Cholinergic Agonists; Electrophoresis, Polyacrylamide Gel; Enzyme Precursors; Female; Galactosyltransferases; Golgi Apparatus; Histocompatibility Antigens Class II; Immunoblotting; Membrane Proteins; rab GTP-Binding Proteins; rab5 GTP-Binding Proteins; Rabbits; Sjogren's Syndrome; Sodium-Potassium-Exchanging ATPase; Stimulation, Chemical

Elevated level of serum prostatic acid phosphatase (PAP) activity in a patient with Sjogren's syndrome was found to be due to the presence of PAP-immunoglobulin complexes in circulation. The patient did not have a prostatic malignancy. The complexes were demonstrated by counter-immunoelectrophoresis, protein A-Sepharose immunoprecipitation and agarose-gel electrophoresis. Free enzyme was not detected in serum, and the activity of the complexed enzyme was probably unaltered on binding with the immunoglobulins.

Topics: Acid Phosphatase; Aged; Antigen-Antibody Complex; Chemical Precipitation; Counterimmunoelectrophoresis; Electrophoresis, Agar Gel; Humans; Immunoglobulins; Male; Prostate; Sjogren's Syndrome

Topics: Acid Phosphatase; Female; Humans; Male; Middle Aged; Parotid Gland; Phosphates; Potassium; Saliva; Secretory Rate; Sjogren's Syndrome; Sodium

Topics: Acid Phosphatase; Adolescent; Adult; Biopsy; Blind Loop Syndrome; Female; Gastrectomy; Gastric Juice; Glucose-6-Phosphatase; Histocytochemistry; Humans; Hyperthyroidism; Intestinal Mucosa; Intestine, Small; Iodine Isotopes; Lipase; Liver Diseases; Male; Sjogren's Syndrome; Succinate Dehydrogenase; Triolein