Evidence for immunoglobulin Fc receptor-mediated prostaglandin2 and platelet-activating factor formation by cultured rat mesangial cells

Journal Article · Thu Sep 01 00:00:00 EDT 1988 · J. Clin. Invest.; (United States)

DOI:https://doi.org/10.1172/JCI113701· OSTI ID:6682018

Neuwirth, R; Singhal, P; Diamond, B; Hays, R M; Lobmeyer, L; Clay, K; Schlondorff, D

The possibility of Fc-dependent uptake of IgG immune complexes was examined in subcultured rat mesangial cells free of monocytes. 195Au-labeled colloidal gold particles were coated either with BSA only or with BSA followed by rabbit anti-BSA-IgG or the F(ab')2 fragment of the IgG. Mesangial cells preferentially took up 195Au particles covered with BSA-anti-BSA-IgG over those covered with BSA or the F(ab')2 fragment. This uptake was a time-dependent and saturable process inhibitable by sodium azide or cytochalasin B. Using phase-contrast microscopy in the light reflectance mode, it was established that essentially all mesangial cells took up IgG-coated gold particles. By electron microscopy the process was shown to consist of vesicular uptake with delivery to endosomes. Mesangial binding-uptake of the IgG-covered particles was associated with stimulation of PGE2 synthesis and production of platelet-activating factor, a lipid mediator of inflammation. To characterize the potential Fc receptor for IgG we used the rosetting technique with sheep red blood cells coated with IgG subclass-specific mouse monoclonal antibodies. 50% of mesangial cells exhibited rosetting with red cells coated with mouse IgG2a, whereas negligible rosetting was observed with IgG2b or IgG1. Competition experiments confirmed the specificity of IgG2a binding. We conclude that cultured rat mesangial cells exhibit specific receptors for IgG and that occupancy of Fc receptors results in endocytosis and is associated with generation of PGE2 and platelet-activating factor. These observations may be of significance for immune-mediated glomerular diseases.

• Research Organization: Albert Einstein College of Medicine, Bronx, NY (USA)
• OSTI ID: 6682018
• Journal Information: J. Clin. Invest.; (United States), Vol. 82:3
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BLOOD COAGULATION FACTORS
BIOSYNTHESIS
IMMUNOGLOBULINS
RECEPTORS
PROSTAGLANDINS
BIOCHEMICAL REACTION KINETICS
CELL CULTURES
ELECTRON MICROSCOPY
GOLD 195
MONOCLONAL ANTIBODIES
RATS
TIME DEPENDENCE
TRACER TECHNIQUES
UPTAKE
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
COAGULANTS
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
GLOBULINS
GOLD ISOTOPES
HEAVY NUCLEI
HEMATOLOGIC AGENTS
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MICROSCOPY
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SECONDS LIVING RADIOISOTOPES
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques