Fab fragments (Fabs) of antibodies have the ability to bind to specific allergens but lack the Fc portion that exerts effector functions via binding to receptors including FcεR1 on mast cells. In the present study, we investigated whether intranasal administration of the effector function-lacking Fabs of a monoclonal antibody IgG1 (mAb, P1-8) to the major allergen Cry j1 of Japanese cedar pollen (JCP) suppressed JCP-induced allergic rhinitis in mice.
Balb/c mice sensitized with JCP on days 0 and 14 were challenged intranasally with the pollen on days 28, 29, 30 and 35. Fabs prepared by the digestion of P1-8 with papain were also administered intranasally 15 min before each JCP challenge.
Intranasal administration of P1-8 Fabs was followed by marked suppression of sneezing and nasal rubbing in mice with JCP-induced allergic rhinitis. The suppression of these allergic symptoms by P1-8 Fabs was associated with decreases in mast cells and eosinophils and decreased hyperplasia of goblet cells in the nasal mucosa.
These results demonstrated that intranasal exposure to P1-8 Fabs was effective in suppressing JCP-induced allergic rhinitis in mice, suggesting that allergen-specific mAb Fabs might be used as a tool to regulate allergic pollinosis.
BACKGROUND AND PURPOSE Fab fragments (Fabs) of antibodies maintain the ability to bind specific antigens, but lack the binding site for complement as well as the site for binding to receptors on effector cells, such as macrophages that play an important role in inflammation. In the present study, we investigated whether Fabs specific for ovalbumin (OVA) were specifically able to suppress anti-OVA antibody-mediated arthritis (AOA-MA) in mice.
EXPERIMENTAL APPROACH AOA-MA was induced by i.v. injection of purified anti-OVA antibodies into naïve mice followed by intra-articular (left ankle) challenge with the antigen. Anti-OVA Fabs prepared by digestion of anti-OVA antibodies with papain were injected i.v. immediately after administration of the intact antibodies. Normal Fabs were used as a control. Arthritis was assessed by thickness of the joints (caliper) and by histology of paw sections, stained with haematoxylin and eosin.
KEY RESULTS AOA-MA was markedly suppressed by anti-OVA Fabs, but not by control Fabs. Histologically, mice treated with control Fabs showed marked oedema of synovial tissues with a large number of inflammatory cells including neutrophils, whereas animals given anti-OVA Fabs had mild oedema of the synovium and sparse infiltration of such cells. The antigen-specific suppression of joint inflammation by anti-OVA Fabs was associated with reduced consumption of complement. In vitro studies showed that anti-OVA Fabs significantly blocked the binding of intact anti-OVA antibodies to OVA.
CONCLUSIONS AND IMPLICATIONS Antibody-mediated arthritis appears to be specifically down-regulated by Fabs that competitively inhibit the binding of antibodies to antigens.
We investigated the effect of bisphenol A (BPA), which binds estrogen receptors, on immune responses including production of antigen-specific antibodies, proliferative responses of lymphoid cells, and Th1 and Th2 responses.
For this investigation, mice were p.o. given varying doses including 3, 30, 300, and 3000 μg kg−1 of BPA immediately after immunization with hen egg lysozyme (HEL) (day 0) and then daily by day 20. On day 21, anti-HEL IgG antibodies in sera and proliferative responses of spleen cells to the antigen were measured. Anti-HEL IgG2a antibodies and IFN-γ secreted from splenic lymphocytes were also measured as indicators of Th1 immune responses, while anti-HEL IgG1 antibodies and IL-4, as those of Th2 responses.
The results showed that treatment with 3000 μg kg−1 of BPA was followed by a significant increase in anti-HEL IgG as well as the antigen-specific cell proliferation. Anti-HEL IgG2a production and IFN-γ secretion were significantly enhanced in mice treated with 300 and 30 μg kg−1 of BPA, respectively, while anti-HEL IgG1 production and IL-4 secretion were augmented in animals given 3000 and 300 μg kg−1 of the chemical, respectively.
Augmentation of these immune responses was also observed in mice exposed to 0.3–30 μg kg−1 of estradiol, although Th1 responses appeared to be more sensitive to the sex hormone than Th2 responses.
These results suggest that BPA may play a role in augmenting immune responses, especially Th1 responses.
We investigated the effect of bisphenol A (BPA), which binds estrogen receptors, on immune responses including production of antigen-specific antibodies, proliferative responses of lymphoid cells, and Th1 and Th2 responses.
For this investigation, mice were p.o. given varying doses including 3, 30, 300, and 3000 μg kg−1 of BPA immediately after immunization with hen egg lysozyme (HEL) (day 0) and then daily by day 20. On day 21, anti-HEL IgG antibodies in sera and proliferative responses of spleen cells to the antigen were measured. Anti-HEL IgG2a antibodies and IFN-γ secreted from splenic lymphocytes were also measured as indicators of Th1 immune responses, while anti-HEL IgG1 antibodies and IL-4, as those of Th2 responses.
The results showed that treatment with 3000 μg kg−1 of BPA was followed by a significant increase in anti-HEL IgG as well as the antigen-specific cell proliferation. Anti-HEL IgG2a production and IFN-γ secretion were significantly enhanced in mice treated with 300 and 30 μg kg−1 of BPA, respectively, while anti-HEL IgG1 production and IL-4 secretion were augmented in animals given 3000 and 300 μg kg−1 of the chemical, respectively.
Augmentation of these immune responses was also observed in mice exposed to 0.3–30 μg kg−1 of estradiol, although Th1 responses appeared to be more sensitive to the sex hormone than Th2 responses.
These results suggest that BPA may play a role in augmenting immune responses, especially Th1 responses.
British Journal of Pharmacology (2003) 138, 1271–1276. doi:10.1038/sj.bjp.0705166
The present study was undertaken to study the effect of the nonsteroidal anti-inflammatory drug indomethacin on Th1 and Th2 immune responses. For this study, mice were immunized by s.c. injection of ovalbumin (OVA) emulsified with complete Freund's adjuvant into the base of the tail (day 0). Varying doses of indomethacin were orally administrated daily from days 0 to 20. On day 21, anti-OVA IgG2a and interferon-γ as an indicator of Th1 responses and anti-OVA IgG1 and interleukin-10 as that of Th2 responses were measured. The results showed that treatment with indomethacin was followed by decreases in OVA-specific IgG and proliferation of spleen cells to the antigen. Indomethacin inhibited both Th1 and Th2 responses, although the nonsteroidal anti-inflammatory drug suppressed the former more effectively than the latter. Administration of indomethacin resulted in suppression of antigen (OVA)-induced arthritis that was associated with inhibition of anti-OVA IgG2a but not IgG1 production. These results suggest that nonsteroidal anti-inflammatory drugs may downregulate Th1 and, to a lesser extent, Th2 immune responses. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:1723–1729, 2003
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