PMID- 15286662
OWN - NLM
STAT- MEDLINE
DCOM- 20041014
LR  - 20230216
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 84
IP  - 10
DP  - 2004 Oct
TI  - AL-amyloidosis and light-chain deposition disease light chains induce divergent 
      phenotypic transformations of human mesangial cells.
PG  - 1322-38
AB  - 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.
FAU - Keeling, John
AU  - Keeling J
AD  - Department of Pathology, Louisiana State University Health Sciences, Shreveport, 
      LA 71130, USA.
FAU - Teng, Jiamin
AU  - Teng J
FAU - Herrera, Guillermo A
AU  - Herrera GA
LA  - eng
GR  - P41 RR003155/RR/NCRR NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Actins)
RN  - 0 (Amyloid)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (Biomarkers)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Immunoglobulin Light Chains)
SB  - IM
MH  - Actins/metabolism
MH  - Amyloid/*immunology/metabolism
MH  - Amyloidosis/*immunology/metabolism/pathology
MH  - Antigens, CD/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/metabolism
MH  - Biomarkers/analysis
MH  - Cells, Cultured
MH  - Extracellular Matrix Proteins/metabolism
MH  - Glomerular Mesangium/*drug effects/metabolism/ultrastructure
MH  - Humans
MH  - Immunoglobulin Light Chains/metabolism/*pharmacology
MH  - Immunohistochemistry
MH  - Kidney Diseases/*immunology/metabolism/pathology
MH  - Multiple Myeloma/immunology/metabolism/pathology
MH  - Phenotype
EDAT- 2004/08/03 05:00
MHDA- 2004/10/16 09:00
CRDT- 2004/08/03 05:00
PHST- 2004/08/03 05:00 [pubmed]
PHST- 2004/10/16 09:00 [medline]
PHST- 2004/08/03 05:00 [entrez]
AID - S0023-6837(22)60192-2 [pii]
AID - 10.1038/labinvest.3700161 [doi]
PST - ppublish
SO  - Lab Invest. 2004 Oct;84(10):1322-38. doi: 10.1038/labinvest.3700161.