AL-amyloidosis and light-chain deposition disease light chains induce divergent phenotypic transformations of human mesangial cells.
Human mesangial cells (HMCs) are injured by either excessive amounts or abnormal light chains (LCs), or a combination of both in patients with plasma cell dyscrasias. Consequently, these HMCs undergo phenotypic transformations. HMCs were incubated with eight different light-chains (LCs) for 96 h. These cells, in addition to 51 patient samples from patients with AL-amyloidosis (AL-Am), light-chain deposition disease (LCDD), myeloma cast nephropathy (MCN) and controls were analyzed by immunohistochemistry for CD68, muscle-specific actin (MSA), smooth muscle actin (SMA), CD14, and Ham56 protein expressions. All samples were also studied using electron microscopy. Greater staining (four- and three-fold) expressions of CD68 and Ham56, respectively, were observed in the HMCs incubated with AL-Am-LCs compared to those with LCDD-LCs and control. SMA expression levels were five-fold higher in LCDD-LC-treated cells compared to the other categories of LC-treated and control cells. Similar results were obtained in the renal specimens, however, CD68 levels were 12-fold higher in the AL-Am cases compared to the LCDD cases, respectively. Conversely, MSA and SMA levels were three fold higher in the LCDD cases than in the AL-Am ones. No CD14 expression was noted in any of the samples and CD-34 staining of HMCs treated with the various LCs only showed rare positive cells. Dynamic real-time studies to visualize the rough endoplasmic reticulum (RER) and lysosomal compartments in HMCs incubated with LCDD and AL-Am-LCs showed striking expansion of each of the above-mentioned compartments, respectively. This indicates the presence of more RER in the LCDD-LC-treated HMCs and a striking increase in lysosomes noticeable in the AL-Am-LC-treated cells. Data obtained in this study highlighted that HMCs incubated with LCDD-LCs undergo a myofibroblastic phenotypic transformation, while AL-Am-LCs induce a macrophage-like phenotype in these cells.
Keeling
John
J
Department of Pathology, Louisiana State University Health Sciences, Shreveport, LA 71130, USA.
Teng
Jiamin
J
Herrera
Guillermo A
GA
D000199:Actins / Q000378:metabolism; D000682:Amyloid / Q000276:immunology* / Q000378:metabolism; D000686:Amyloidosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism / Q000494:pharmacology*; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D000097382:CD68 Molecule
D000199:Actins; D000682:Amyloid; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D007147:Immunoglobulin Light Chains; C067980:CD68 antigen, human; D000097382:CD68 Molecule