Modulatory Effects of Freund’s Adjuvant Treatment on Mast Cell Histamíne Release and Homocytotropic Antibody Synthesis

Abstract

The present study examines the influence of Freund’s complete adjuvant (FCA) injections on sensitized PVG rats with respect to (1) serum levels of IgE and IgG_2α antibodies and total IgE (all assessed by radioimmunoassays) and (2) the capacity of serosal mast cells to release histamine on challenge in vitro with ‘immunological’ secretagogues (specific antigen, anti-IgE, concanavalin A) or with compound 48/80. The rats were immunized with 10 μg ovalbumin (OA); alum, Bordetella pertussis vaccine, or silica gel were employed as adjuvants. Treatment with FCA was performed by single intraperitoneal injections 3, 2, or 1 week(s) before or 1 or 2 weeks after sensitization. Tests were conducted 3 weeks after sensitization. The results show that the effect of FCA treatment varied reproducibly with the adjuvant employed for sensitization and with the timing of the FCA administration. FCA treatment could either increase, fail to affect, or decrease total serum IgE and OA-IgG_2α antibody levels as well as serosal mast cell responsiveness, whereas OA-IgE antibody responses were decreased or not affected. Moreover, serum levels of OA-IgE and OA-IgG_2α antibodies and total IgE were affected by FCA treatment independently of each other. Finally, serosal mast cell responsiveness to a given secretagogue could be influenced by the FCA treatment apparently independently of that to other secretagogues. A salient finding was that effects of FCA treatment on mast cell responsiveness did not necessarily conform to effects on antibody synthesis. Collectively, these data support the opinion that the mechanisms of action of the IgE-promoting adjuvants employed differ and suggest that the expression of serosal mast cell responsiveness to each examined secretagogue can be regulated separately. They also suggest that the serosal mast cell sensitizing capacity of homocytotropic antibodies may not be adequately quantified by immunochemical methods employing reagents prepared against IgE and IgG_2α protein.

Inhibition of an IgE response by secondary B cells of a different isotype.

“…A strong and selective inhibitory effect of preinoculation of CFA on IgE anti-OVA production was noted by Smith and Butchko (29) in both high-or moderate-responder mice . The difference in our results may be attributable to differences in timing of administration of CFA and antigen, which was shown to be a critical factor in one system investigated (30) .…”

Bradykinin-evoked scratching responses in complete Freund's adjuvant-inflamed skin through activation of B1 receptor

“…The early inflammation induced by CFA has been shown to be mast cell–dependent. 25 The mechanism of itch induced by CFA in the acute phase should be investigated further. We found that BK dose-dependently evoked scratching responses in the CFA-inflamed area.…”

Is There a Functional Heterogeneity among IgE‐Type Mast Cell‐Sensitizing Antibodies?

“…This was apparently not due to a nonspecific effect of FGA since responsiveness of the cells to compound 48/80 or to anti-IgE was not affected (13), and an analogous treatment with FCA of animals immunized with Silica gel, if anything, decreased mast cell responsiveness to antigen (13). Even more unexpectedly, if animals to be immunized with OA together with Perthydra] were treated with FCA 1 week before immunization, they had lower IgE-antibody levels but higher mast cell responsiveness to OA (but not to ConA or 48/ 80) than saline-treated eontrols 3 weeks after immunization (13). Thus, one can modulate, by suitable FCA-treatment of animals, serosal mast cell responsiveness to antigen and OA-IgE-antibody serum levels in opposite direetions.…”

“…We have examined ihe correlation between serosal mast eell, lung, and tracheal tissue responsiveness lo aniigen and scrum OA-lglv aniilKKly levels in seveial ral .sitain.s (10,12,13). Tlie lader vat'iablc wa.s examined by iaclitjiiiununt)a.s.say in solid pha.sc performance, utilizing reagenis prepared wilh th<' aid ol myeloma proieins (7, .…”

“…We have examined the influence of injections of Freund's complete adjuvant (FCA) on serosal mast cell responsiveness and IgE-antibody (and IgGjj-antibody) levels in PVG rats immunized with OA in alum (13). The following results merit consideration (see Fig.…”