[3H]PK11195 binding sites in human neutrophils: effect of fMLP stimulation and modulation in rheumatic diseases.
OBJECTIVE
The objectives of this study were to evaluate the [3H]PK11195 binding parameters in a model of acute inflammation, the N-formylmethionine-leucine-phenylalanine (fMLP)-stimulated neutrophil cell membranes, and to analyze if alterations of peripheral-type benzodiazepine receptor (PBR) characteristics occurred in neutrophil cell membranes of patients affected by osteoarthritis (OA), rheumatoid arthritis (RA), and psoriasic arthritis (PA).


METHODS
Neutrophils were obtained from 15 patients with OA, 15 patients with RA, and 15 patients with PA. fMLP stimulation was performed to aliquots of neutrophils from six healthy individuals. Evaluation of kinetic parameters of PBR was performed using [3H]PK11195, as specific radioligand compared with 15 healthy volunteers.


RESULTS
The results showed a significant decrease of Kd and Bmax in fMLP-stimulated neutrophil membranes. Moreover, an increase of PBR binding sites and affinity value was observed in neutrophils membranes from PA patients.


CONCLUSIONS
Our data suggested a fMLP modulation on [3H]PK11195 binding in human neutrophils. Moreover, our results showed an up-regulation of PBR in neutrophils of PA patients.
Giusti
Laura
L
Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy.
Betti
Laura
L
Giannaccini
Gino
G
Mascia
Giovanni
G
Bazzichi
Laura
L
Lucacchini
Antonio
A
D000368:Aged; D015535:Arthritis, Psoriatic / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood*; D001665:Binding Sites; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*; D010003:Osteoarthritis / Q000097:blood; D011963:Receptors, GABA-A / Q000378:metabolism
D007546:Isoquinolines; D011963:Receptors, GABA-A; D009240:N-Formylmethionine Leucyl-Phenylalanine; C037850:PK 11195