PMID- 10438958
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20171116
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 4
DP  - 1999 Aug 15
TI  - CD40 ligand-activated human monocytes amplify glomerular inflammatory responses 
      through soluble and cell-to-cell contact-dependent mechanisms.
PG  - 2168-75
AB  - Monocytes/macrophages play a critical role in the initiation and progression of a 
      variety of glomerulonephritides. We sought to define the interactions between 
      physiologically activated human monocytes and glomerular mesangial cells (MC) by 
      employing a cell culture system that permits the accurate assessment of the 
      contribution of soluble factors and cell-to-cell contact. Human peripheral blood 
      monocytes, primed with IFN-gamma and GM-CSF, were activated with CD40 ligand 
      (CD40L) or TNF-alpha and cocultured with MC. CD40L-activated monocytes induced 
      higher levels of IL-6, monocyte chemoattractant protein-1 (MCP-1) and ICAM-1 
      synthesis by MC. Separation of CD40L-activated monocytes from MC by a porous 
      membrane decreased the mesangial synthesis of IL-6 by 80% and ICAM-1 by 45%, but 
      had no effect on MCP-1. Neutralizing Abs against the beta 2 integrins, LFA-1 and 
      Mac-1, decreased IL-6 production by 40 and 50%, respectively. Ligation of 
      mesangial surface ICAM-1 directly enhanced IL-6, but not MCP-1, production. 
      Simultaneous neutralization of soluble TNF-alpha and IL-1 beta decreased MCP-1 
      production by 55% in membrane-separated cocultures of MC/CD40L-activated 
      monocytes. Paraformaldehyde-fixed CD40L-activated monocytes (to preserve membrane 
      integrity but prevent secretory activity), cocultured with MC at various ratios, 
      induced IL-6, MCP-1, and ICAM-1 synthesis by MC. Plasma membrane preparations 
      from activated monocytes also induced mesangial IL-6 and MCP-1 synthesis. The 
      addition of plasma membrane enhanced TNF-alpha-induced mesangial IL-6 production 
      by approximately 4-fold. Together, these data suggest that the CD40/CD40L is 
      essential for optimal effector function of monocytes, that CD40L-activated 
      monocytes stimulate MC through both soluble factors and cell-to-cell contact 
      mediated pathways, and that both pathways are essential for maximum stimulation 
      of MC.
FAU - Kuroiwa, T
AU  - Kuroiwa T
AD  - Arthritis and Rheumatism Branch, National Institute of Arthritis and 
      Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA. 
      kuroiwat@arb.niams.nih.gov
FAU - Lee, E G
AU  - Lee EG
FAU - Danning, C L
AU  - Danning CL
FAU - Illei, G G
AU  - Illei GG
FAU - McInnes, I B
AU  - McInnes IB
FAU - Boumpas, D T
AU  - Boumpas DT
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD18 Antigens)
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - CD18 Antigens/physiology
MH  - CD40 Antigens/*physiology
MH  - CD40 Ligand
MH  - Cell Communication/*immunology
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis
MH  - Coculture Techniques
MH  - Glomerular Mesangium/metabolism
MH  - Glomerulonephritis/*immunology/metabolism/*pathology
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/biosynthesis/immunology/metabolism/physiology
MH  - Interleukin-1/antagonists & inhibitors/biosynthesis/immunology
MH  - Interleukin-12/biosynthesis
MH  - Interleukin-6/biosynthesis
MH  - Ligands
MH  - Macrophage Activation
MH  - Membrane Glycoproteins/*physiology
MH  - Monocytes/*immunology/metabolism
MH  - Signal Transduction/immunology
MH  - Solubility
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/biosynthesis/immunology
EDAT- 1999/08/10 00:00
MHDA- 1999/08/10 00:01
CRDT- 1999/08/10 00:00
PHST- 1999/08/10 00:00 [pubmed]
PHST- 1999/08/10 00:01 [medline]
PHST- 1999/08/10 00:00 [entrez]
AID - ji_v163n4p2168 [pii]
PST - ppublish
SO  - J Immunol. 1999 Aug 15;163(4):2168-75.