Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-9-9
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2168-75
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10438958-Antigens, CD18, pubmed-meshheading:10438958-Antigens, CD40, pubmed-meshheading:10438958-CD40 Ligand, pubmed-meshheading:10438958-Cell Communication, pubmed-meshheading:10438958-Cells, Cultured, pubmed-meshheading:10438958-Chemokine CCL2, pubmed-meshheading:10438958-Coculture Techniques, pubmed-meshheading:10438958-Glomerular Mesangium, pubmed-meshheading:10438958-Glomerulonephritis, pubmed-meshheading:10438958-Humans, pubmed-meshheading:10438958-Intercellular Adhesion Molecule-1, pubmed-meshheading:10438958-Interleukin-1, pubmed-meshheading:10438958-Interleukin-12, pubmed-meshheading:10438958-Interleukin-6, pubmed-meshheading:10438958-Ligands, pubmed-meshheading:10438958-Macrophage Activation, pubmed-meshheading:10438958-Membrane Glycoproteins, pubmed-meshheading:10438958-Monocytes, pubmed-meshheading:10438958-Signal Transduction, pubmed-meshheading:10438958-Solubility, pubmed-meshheading:10438958-Tumor Necrosis Factor-alpha
pubmed:year
1999
pubmed:articleTitle
CD40 ligand-activated human monocytes amplify glomerular inflammatory responses through soluble and cell-to-cell contact-dependent mechanisms.
pubmed:affiliation
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA. kuroiwat@arb.niams.nih.gov
pubmed:publicationType
Journal Article