Elevated serum levels in human pregnancy of a molecule immunochemically similar to eosinophil granule major basic protein.

Abstract

In 1956 Gansler (1) observed infiltration of the rat uterus by eosinophils coincident with the estrus cycle. This observation was confirmed and extended by the work of Bassett (2) and Ross and Klebanoff (3). Since then, various investigations have shown (a) that injection of estrogen into castrated or immature rodents leads to immediate uterine eosinophilia (4-10), (b) that the uterine eosinophil is marrow derived (11), (c) that the uterine eosinophil number varies >100-fold during the normal estrus cycle (12), (d) that uterine content of eosinophil peroxidase varies directly with the estrus cycle (13,14), (e) that eosinophils possess a unique cell surface estrogen receptor (4-9), and (f) that estrogen-induced uterine eosinophilia apparently has no dependence upon uterine mast cell activity (15-18).In contrast, there are few observations relating eosinophils to human reproductive physiology . Cyclic eosinopenia correlating with ovulation has been reported (19-21) and cyclic variations in endometrial eosinophils and their uptake of tritiated estradiol have also been observed (22). However, no role for the eosinophil in normal human reproduction is presently recognized . During the course of studies of hypersensitivity diseases in pregnancy we found that serum levels of a molecule immunochemically similar to the eosinophil granule major basic protein (MBP)' were elevated in all pregnant women, increasing during pregnancy and decreasing to normal levels after parturition. Because eosinophilia is not a feature of normal pregnancy, and serum levels of other eosinophil proteins are not elevated, the results of this study suggest that the immunoreactive MBP in pregnancy serum is derived from a source other than the eosinophil . Materials and MethodsDithiothreitol, iodoacetamide, equine liver catalase, sodium borate, boric acid, Staphylococcus aureus protein A, chloramine T, protamine sulfate, bovine serum albumin, Trizma

The proform of eosinophil major basic protein: a new maternal serum marker for Down syndrome

“…Briefly, serum samples were reduced and alkylated (Maddox et al, 1983) and added to microtitre wells coated with the catching mouse monoclonal antibody J13-6B6. Following incubation and washing, bound proMBP was detected with 125 I-labelled mouse monoclonal antibody J14-8A2.…”

“…MBP antigen has previously been determined immunochemically (Maddox et al, 1983;Wasmoen et al, 1987Wasmoen et al, , 1989Wasmoen et al, , 1991Wagner et al, 1993). MBP is a 117 residue cationic polypeptide and the proform (proMBP) has a highly glycosylated 88 residue N-terminal extension , making the proBMP far less cationic and abolishing the toxicity of MBP (Barker et al, 1988;Popken-Harris et al, 1995).…”

Localization of eosinophil granule major basic protein in human basophils.

“…4), MBP levels in basophii extracts were measured using a two-site immunoradiometric assay (TSIRA) (34) as described in detail elsewhere (35). Briefly, protein A-purified rabbit IgG anti-MBP antibody was bound to plastic wells of a Microelisa 96-well flexible plastic plate (Dynatech Laboratories, Inc., Freehold, NJ), incubated with dilutions of reduced and aikylated basophil extract or MBP standard, and, after extensive washing, the resulting bound MBP was detected by adding radiolabeled ~5I-ACP anti-MBP.…”

Reproductive immunology: biomarkers of compromised pregnancies.

“…MBP blood levels rise by 6 weeks of gestation and return to normal by 6 weeks postpartum (50) (Fig. 2).…”

“…In human pregnancy, MBP increases in peripheral blood independent of either eosinophils or other eosinophil proteins (50), and has been shown by using immunohistological techniques to be localized in extravillous trophoblast (51). Pregnancyassociated MBP has been purified from human placentae.…”