Monocyte activation in rheumatoid arthritis (RA): increased integrin, Fc gamma and complement receptor expression and the effect of glucocorticoids.
The aim of this work was to study the expression of beta 1- and beta 2-integrins, CR1, CD44 and Fc gamma receptors on peripheral blood monocytes in RA. The expression of these receptors was measured by flow cytometry, before and after treatment with low-dose prednisolone. Expression of the same receptors was also measured before and after treatment with metyrapone, a substance that inhibits the synthesis of cortisol in the adrenals. The expression of the beta 2-integrins CD11a, CD11b and CD18, of CD35 (CR1), and of Fc gamma RII and Fc gamma RI (CD32 and CD64) on monocytes was elevated in the RA patients compared with healthy controls, while the expression of the beta 1-integrins (CD29, CD49d, CD49f) was unaffected. A significant correlation between monocyte expression of CD64 and C-reactive protein (CRP), and blood platelet count, respectively, was found in the group of patients with RA. After 4-6 weeks of treatment with low-dose prednisolone, the expression on the monocytes of CD11a, CD11b, CD18, CD35, CD32 and CD64 was normalized. A significant correlation (r = 0.64, P = 0.02) was found between the decrease in expression of CD11b and clinical improvement after prednisolone treatment. Two days of metyrapone treatment, which significantly lowered the serum cortisol levels, elevated the expression of CD35 and CD49f. Priming of peripheral monocytes seems to be one of the mechanisms behind the recruitment of monocytes to the rheumatoid synovium. One reason for the good clinical effects of prednisolone in RA could be a down-regulation of adhesion and phagocytosis receptors on monocytes.
Torsteinsdóttir
I
I
Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
Arvidson
N G
NG
Hällgren
R
R
Håkansson
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D018821:CD18 Antigens / Q000097:blood; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D019012:Integrin beta1 / Q000097:blood; D016023:Integrins / Q000097:blood*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011239:Prednisolone / Q000494:pharmacology*; D011951:Receptors, Complement / Q000097:blood*; D017452:Receptors, IgG / Q000097:blood*
D018821:CD18 Antigens; D005938:Glucocorticoids; D019012:Integrin beta1; D016023:Integrins; D011951:Receptors, Complement; D017452:Receptors, IgG; D011239:Prednisolone; D006854:Hydrocortisone; D008797:Metyrapone