PMID- 17245394
OWN - NLM
STAT- MEDLINE
DCOM- 20070605
LR  - 20071115
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 71
IP  - 6
DP  - 2007 Mar
TI  - Interaction between proximal tubular epithelial cells and infiltrating 
      monocytes/T cells in the proteinuric state.
PG  - 526-38
AB  - We hypothesize an interaction between T cells/monocytes and the tubules in the 
      development of tubulointerstitial injury in chronic proteinuric nephropathy. We 
      established in vitro co-culture systems of proximal tubular epithelial cells 
      (PTEC) and T cells/monocytes to study the contribution of soluble factors and 
      cell-to-cell contact in the development of tubulointerstitial injury. The release 
      of monocyte chemoattractant protein-1 (MCP1 or CCL2), Regulated upon Activation, 
      normal T cell Expressed and Secreted (RANTES or CCL5), soluble intracellular 
      adhesion molecules-1 (sICAM-1), or interleukin-6 (IL-6) was increased in PTEC 
      following apical exposure to human serum albumin (HSA). The release of CCL2, 
      CCL5, or sICAM-1 from PTEC was enhanced by contact of monocytes/T cells on the 
      basolateral surface. Tumor necrosis factor-alpha (TNF-alpha) and IL-1beta are 
      important soluble factors as suggested by the blocking effect of antibodies (Abs) 
      against TNF-alpha or IL-1beta but not against other cytokines. The percentage of 
      CD4+ T cells expressing both chemokine receptors, CCR2 and CCR5, was increased 
      after culturing with supernatant from the apical or basolateral surface of PTEC 
      following apical exposure to HSA. However, only CCR2 was upregulated in CD8+ T 
      cells, whereas CCR5 expression was increased in monocytes. The chemotaxis of CD4+ 
      or CD8+ T cells to supernatant from PTEC upon apical exposure to HSA was reduced 
      with neutralizing Abs against CCL5 and/or CCL2, whereas the chemotaxis of 
      monocytes was only reduced by anti-CCL5 but not by anti-CCL2. In summary, 
      chemokines released by HSA-activated PTEC are amplified by monocytes/T cells. 
      Mediators released by HSA-activated PTEC can differentially modulate the 
      expression of chemokine receptors in monocytes/T cells and hence, alter their 
      chemotaxis towards activated PTEC. These interactions are pivotal in the 
      development of tubulointerstitial injury.
FAU - Lai, K N
AU  - Lai KN
AD  - Division of Nephrology, Department of Medicine, Queen Mary Hospital, The 
      University of Hong Kong, Hong Kong, China. knlai@hku.hk
FAU - Leung, J C K
AU  - Leung JC
FAU - Chan, L Y Y
AU  - Chan LY
FAU - Guo, H
AU  - Guo H
FAU - Tang, S C W
AU  - Tang SC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070124
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCL5 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokines, CC)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Serum Albumin)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Cell Communication/*physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism
MH  - Chemokine CCL5
MH  - Chemokines, CC/genetics/metabolism
MH  - Chemotaxis/drug effects/physiology
MH  - Coculture Techniques
MH  - Epithelial Cells/drug effects/metabolism/*pathology
MH  - Gene Expression Regulation/drug effects/physiology
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/genetics/metabolism
MH  - Interleukin-2 Receptor alpha Subunit/genetics/metabolism
MH  - Interleukin-6/genetics/metabolism
MH  - Kidney Tubules, Proximal/drug effects/metabolism/*pathology
MH  - Monocytes/*pathology/physiology
MH  - Proteinuria/*pathology/physiopathology
MH  - Receptors, Chemokine/genetics/metabolism
MH  - Serum Albumin/pharmacology
MH  - T-Lymphocytes/*pathology/physiology
EDAT- 2007/01/25 09:00
MHDA- 2007/06/06 09:00
CRDT- 2007/01/25 09:00
PHST- 2007/01/25 09:00 [pubmed]
PHST- 2007/06/06 09:00 [medline]
PHST- 2007/01/25 09:00 [entrez]
AID - S0085-2538(15)52413-7 [pii]
AID - 10.1038/sj.ki.5002091 [doi]
PST - ppublish
SO  - Kidney Int. 2007 Mar;71(6):526-38. doi: 10.1038/sj.ki.5002091. Epub 2007 Jan 24.