Rj. Dearman et al., Characterization of antibody responses induced in rodents by exposure to food proteins: influence of route of exposure, TOXICOLOGY, 167(3), 2001, pp. 217-231
There is a growing interest in the development of methods to characterize t
he allergenic properties of novel proteins. particularly those expressed by
transgenic crop plants. Approaches to the direct evaluation of allergenic
potential have focused generally on the ability of proteins to induce antib
ody (particularly IgE antibody) after systemic (intraperitoneal; i.p.) or g
avage administration to high IgE responder strain rodents. To date there ha
s been no systematic comparison of the reliability, sensitivity or selectiv
ity of these approaches. We have, therefore, compared antibody (IgG and IgE
) responses induced in Brown Norway (BN) rats by daily gavage administratio
n and in BALB/c strain mice following intraperitoneal or gavage exposure to
food proteins of varying allergenic potential. Animals were exposed to the
allergens peanut agglutinin and ovalbumin (OVA) or to a crude potato prote
in extract (PPE) containing acid phosphatase activity, a common foodstuff w
hich appears to be of low allergenicity. All test proteins were clearly imm
unogenic when administered by gavage to BN rats, with measurable, and in so
me cases very vigorous, IgG antibody responses recorded for all animals. Id
entical exposure of BALB/c strain mice also stimulated detectable IgG antib
ody responses, with particularly high titers recorded following treatment w
ith peanut agglutinin and somewhat less vigorous responses induced by OVA a
nd PPE. Despite these high titer IgG antibody responses, however. none of t
he proteins provoked detectable IgE antibody following gavage administratio
n to BN rats. In contrast, in BALB/c mice oral exposure to peanut agglutini
n elicited high titer IgE antibody, although IgE antibody responses to both
OVA and PPE were much weaker. Parenteral (i.p.) treatment of BAI-Bic strai
n mice with each of the test materials induced relatively high titer IgG an
tibody and a differential potential to stimulate IgE antibody was observed,
High titer IgE responses were provoked by i.p. administration of peanut ag
glutinin and OVA. whereas PPE stimulated little or no detectable IgE antibo
dy. It would appear. therefore, that while it is possible to elicit robust
IgE responses by gavage exposure of BALB/c strain mice to some protein alle
rgens, such as peanut agglutinin, such responses are generally weaker and l
ess consistent than those provoked by i.p. administration. Furthermore, gav
age treatment failed to induce detectable IgE responses in the BN rat, sugg
esting that the ability these animals to mount IgE responses is somewhat va
riable. Following i.p. administration to BALB/c Strain mice, these proteins
displayed immunological properties consistent with what is known of their
allergenic potential in humans. suggesting that, following further evaluati
on with a wider range of proteins, this method may provide one approach to
the identification of potential protein allergens. (C) 2001 Elsevier Scienc
e Ireland Ltd. All rights reserved.