Lysosomal membrane-associated glycoproteins are differentially expressed in acute and chronic human thymic involution

Abstract

The lysosomal membrane-associated glycoproteins LAMP-1 and LAMP-2 are the major constituents of lysosomal membranes with still undefined biological functions. As autophagy is an alternative model of programmed cell death in which lysosomes play a crucial role, we hypothesize that LAMPs might participate in this phenomenon in the involuting thymus. Thymic glands from cases with acute (infection induced) and chronic (senile) involution were examined immunohistochemically for the expression of LAMPs. In acute involution LAMP-1 was localized mainly in medullary epithelial cells, in single macrophages and lymphocytes. Hassall's corpuscules were stained less intensely as compared to control specimens. The quantitative analysis showed a significantly elevated LAMP-2 expression compared to LAMP-1. LAMPs were detected with very slight reactivity in the senile thymus. The enhanced expression of LAMPs, and mainly of LAMP-2, in epithelial cells of incidentally involuted thymus might be an indicator of acute cell injury requiring autophagic degradation of damaged structures. The diminished expression of LAMPs in age-involuted thymus could be a sign of the morphological reorganization and the functional disregulation of the gland. In conclusion, we present novel evidence for differential expression of LAMP-1 and LAMP-2 in thymic involution suggesting their possible involvement in the process of accidental involution of the thymic gland.

Expression of cell cycle and apoptosis regulators in thymus and thymic epithelial tumors

“…HB were stained less intensely as compared with control tissues and the quantitative analysis revealed a significantly increased LAMP-2 expression compared with LAMP-1 [108]. In chronic (senile) involution LAMPs were observed with very slight reactivity [108]. The increased expression of LAMPs, and mainly of LAMP-2, in TEC of thymuses with acute (infection induced) involution might be an indicator of acute cell injury requiring autophagic degradation of damaged structures, and the reduced expression of LAMPs in age-involuted (senile) thymus might be an indicator of the thymic morphological reorganization and the functional dysregulation [108].…”

“…Indeed, in acute (infection induced) involution LAMP-1 was detected mainly in medullary TEC, in single macrophages and thymocytes [108]. HB were stained less intensely as compared with control tissues and the quantitative analysis revealed a significantly increased LAMP-2 expression compared with LAMP-1 [108]. In chronic (senile) involution LAMPs were observed with very slight reactivity [108].…”

“…Indeed, autophagy supports central CD4-positive T cell tolerance through facilitating the presentation of endogenous self-antigens by medullary TEC [8]. The immunohistological expression patterns of lysosome-associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2) were analyzed in thymuses [108,109] since LAMP-2 participates in chaperone-mediated autophagy [110], and evidence was provided for differential expression of LAMP-1 and LAMP-2 in thymic involution [108]. Indeed, in acute (infection induced) involution LAMP-1 was detected mainly in medullary TEC, in single macrophages and thymocytes [108].…”

“…The immunohistological expression patterns of lysosome-associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2) were analyzed in thymuses [108,109] since LAMP-2 participates in chaperone-mediated autophagy [110], and evidence was provided for differential expression of LAMP-1 and LAMP-2 in thymic involution [108]. Indeed, in acute (infection induced) involution LAMP-1 was detected mainly in medullary TEC, in single macrophages and thymocytes [108]. HB were stained less intensely as compared with control tissues and the quantitative analysis revealed a significantly increased LAMP-2 expression compared with LAMP-1 [108].…”

“…In chronic (senile) involution LAMPs were observed with very slight reactivity [108]. The increased expression of LAMPs, and mainly of LAMP-2, in TEC of thymuses with acute (infection induced) involution might be an indicator of acute cell injury requiring autophagic degradation of damaged structures, and the reduced expression of LAMPs in age-involuted (senile) thymus might be an indicator of the thymic morphological reorganization and the functional dysregulation [108]. The expression of the autophagy regulator LC3 was greatly decreased in thymus of 12-and 24-month-old mice as revealed by immunofluorescence microscopy and Western blot analysis, and ultrastructure analysis revealed that the number of autophagic structure/vacuoles in total TEC decreases with age [111].…”