M. Cutolo et al., PRESENCE OF ESTROGEN-BINDING SITES ON MACROPHAGE-LIKE SYNOVIOCYTES AND CD8-LYMPHOCYTES IN NORMAL AND RHEUMATOID SYNOVIUM(, CD29+, CD45RO+ T), Arthritis and rheumatism, 36(8), 1993, pp. 1087-1097
Objective. To study the presence of estrogen-binding sites (EBS) in th
e synovial tissues of male and female patients with rheumatoid arthrit
is (RA) and in age- and sex-matched healthy controls. Methods. Both ty
pe 1 (high affinity, low binding capacity) and type 2 (reduced affinit
y, higher binding capacity) EBS were investigated in both soluble and
nuclear fractions of homogenized synovial tissue samples by a dextran-
coated charcoal method. To determine what type of synovial cell was po
sitive for EBS, cryosections of synovial tissues were immunostained wi
th a specific monoclonal anti-estrogen receptor antibody (anti-ER MAb)
using both immunofluorescence and immunoperoxidase techniques. Double
immunostaining with the anti-ER MAb and with specific MAb to detect d
ifferent macrophage antigens (Ber-MAC3, MAC387, CD68) and CD8+ T cell
subsets (CD29+, CD45RO+ and CD29-, CD45RO-) was performed. Results. Hi
gher affinity EBS were found mostly in nuclear cell fractions of eithe
r RA or control synovial tissues (28 of the 33). These EBS were presen
t to a lesser extent in soluble cell fractions (11 of the 33). Immunos
taining showed the estrogen receptor-positive cells to be the macropha
ge-like synoviocytes and the CD8+, CD29+ T cells both in RA and in con
trol synovial tissues. Higher nuclear content of EBS was consistent wi
th more intense nuclear staining of synoviocytes and T cells. Conclusi
on. It is conceivable that the immunomodulatory activity exerted by es
trogens is at least partly mediated through their interaction with EBS
that are present on macrophage-like synoviocytes, functioning as anti
gen-processing and antigen-presenting cells, and on antigen-experience
d (memory) CD8+ T lymphocytes (CD29+, CD45RO+).