Expression of E-cadherin by murine dendritic cells: E-cadherin as a dendritic cell differentiation antigen characteristic of epidermal Langerhans cells and related cells.

Murine epidermal Langerhans cells (LC) synthesize and express E-cadherin, a homophilic adhesion molecule that mediates adhesion of LC to keratinocytes in vitro. To determine if E-cadherin expression is characteristic of LC or is a feature of all dendritic cells (DC), we studied DC from various lymphoid tissues and peripheral blood for reactivity with anti-E-cadherin monoclonal antibody. By flow cytometry, DC prepared from skin-associated lymph nodes (LN) expressed E-cadherin, whereas DC prepared from gut-associated LN and spleen did not. However, direct comparison revealed that levels of E-cadherin expressed by DC from skin-associated LN were approximately fivefold lower than those expressed by freshly-prepared LC. Immunohistochemical studies confirmed that E-cadherin was expressed by DC in skin-associated LN in situ, and demonstrated that the number of E-cadherin+ DC in LN draining skin previously treated with the contact allergen 2,4,6-trinitrochlorobenzene was increased relative to the number of E-cadherin+ DC present in LN draining normal skin. DC propagated from the blood of cyclophosphamide-treated mice in granulocyte/macrophage-colony stimulating factor-supplemented media also expressed E-cadherin. E-cadherin immunoprecipitated from DC co-migrated in SDS polyacrylamide gels with that from fibroblasts transfected with murine E-cadherin cDNA, and mRNA encoding extracellular and intracellular regions of E-cadherin was present in DC propagated from blood. These results indicate that E-cadherin expressed by murine dendritic cells is identical to E-cadherin expressed by epithelial cells, and suggest that E-cadherin represents a DC differentiation antigen characteristic of LC and lineage-related cells (skin-associated LN DC).

Astrocytes in Alzheimer's disease gray matter express alpha 1-antichymotrypsin mRNA.

The serine protease inhibitor alpha 1-antichymotrypsin (ACT) has been shown to be tightly associated with the amyloid found in plaque cores and blood vessels in the brains of patients with Alzheimer's disease (AD). Although the ACT found in plaques could be derived from the high levels of ACT in serum, previous Northern analysis revealed that ACT mRNA is produced locally in AD gray matter at much higher levels than in control gray matter. To determine which brain cells express ACT mRNA, we conducted in situ hybridization with 35S-labeled cRNA probes on hippocampal sections from four AD and three control cases. To identify astrocytes unequivocally, some of the hybridized sections were immunostained for glial fibrillary acidic protein, which is astrocyte-specific. Our results showed numerous astrocytes that were intensely labeled by the probe for ACT mRNA throughout the subicular gray matter of the AD cases. In contrast, astrocytes in control gray matter were rarely labeled by the probe for ACT mRNA. Examination of plaque cores in the AD subiculum showed that some astrocytes intensely labeled by the probe for ACT mRNA were closely associated with virtually every plaque core. Our results also showed many astrocytes in both AD and control white matter that were intensely labeled by the probe for ACT mRNA, and a small fraction of the astrocytes in a juvenile cerebellar astrocytoma that we examined were found to produce high levels of ACT mRNA. In every area in which astrocytes expressing ACT mRNA were found, astrocytes producing no detectable ACT message were also present. Our findings indicate that astrocytes produce the increased ACT mRNA in AD gray matter observed by Northern analysis, but they also show that ACT mRNA expression by astrocytes is not unique to AD. The presence of astrocytes expressing ACT mRNA near, and extending processes towards, plaque cores strongly suggests that some if not all of the ACT associated with amyloid plaque cores is produced by astrocytes surrounding the cores.