Placenta growth factor (PlGF) induces vascular endothelial growth factor (VEGF) secretion from mononuclear cells and is co-expressed with VEGF in synovial fluid

The aims of this study were (i) to determine whether PlGF, VEGF and PlGF/VE GF heterodimers are detected in synovial fluid (SF) and plasma samples from patients with a range of arthropathies; (ii) to describe whether any corre lation exists between SF PlGF, VEGF and PlGF/VEGF heterodimer levels and th e total and differential SF leucocyte counts; and (iii) to investigate the regulation of peripheral blood mononuclear cell (PBMC) VEGF secretion by st imuli relevant to inflammatory joints. PlGF, VEGF and PlGF/VEGF heterodimer levels were measured in the SF and plasma of patients with a range of arth ropathies and normal controls by ELISA. Western blotting for PlGF was perfo rmed on SF from three patients with rheumatoid arthritis (RA) and primary i nflammatory arthropathies. VEGF was quantified in cell culture supernatants after stimulation with lipopolysaccharide (LPS), PlGF or cobalt ions of PB MC isolated from RA patients and controls. PlGF and VEGF were detected in a ll SF samples. PlGF/VEGF heterodimers were detected in 10.2% of SF samples, most frequently in RA samples. Western blotting confirmed the presence of PlGF in RA SF. PlGF was detected in 52% of RA and 31% of control plasma sam ples, and VEGF was detected in 38% of RA and 38% of control plasma samples. PlGF/VEGF heterodimers were detected in 21% of RA samples and none of the control samples. In primary inflammatory arthropathy patients, SF PlGF and VEGF levels correlated significantly with the SF total leucocyte count and the neutrophil count. PlGF was the most potent inducer of PBMC VEGF product ion in both RA and control subjects. This is the first report of the detect ion of PlGF and PlGF/VEGF heterodimers in the SF of patients with inflammat ory arthropathies, and we have shown for the first time that PlGF up-regula tes PBMC VEGF production. PlGF may therefore play a key role in the product ion of VEGF in the inflammatory joint.