Localization of a molecule immunochemically similar to eosinophil major basic protein in human placenta.

We have recently reported that human pregnancy is characterized by a 10- to 20-fold elevation of eosinophil major basic protein (MBP) immunoreactivity in maternal blood. Here we show, by immunofluorescence, that placental tissue specifically binds antibody to MBP in and around the placental X cells and placental-site giant cells and, using thin plastic sections, that placenta has no infiltrating eosinophils. The X cells line the inner aspects of placental septal cysts, and the cyst fluid, obtained by aspiration, contains immunoreactive MBP at concentrations of 100 micrograms/ml, a sixfold greater concentration than the highest levels measured in maternal blood. The soluble MBP immunoreactivities in placental homogenates and in maternal serum chromatograph identically on Sephadex G-50, and both these gestational MBP molecules migrate as though substantially larger than the MBP found in serum from patients with hypereosinophilic syndrome or purified from the eosinophil granule. Our inability to demonstrate eosinophils in maternal blood or placental tissue, coupled with the large quantities of immunoreactive MBP highly localized in placental cysts and the chromatographic behavior of this molecule, suggest that the MBP detected in human gestation is produced by placenta.

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

Prenatal Diagnosis ◽

10.1002/(sici)1097-0223(199910)19:10<905::aid-pd658>3.0.co;2-q ◽

1999 ◽

Vol 19 (10) ◽

pp. 905-910 ◽

Cited By ~ 20

Author(s):

Michael Christiansen ◽

Claus Oxvig ◽

Jill M. Wagner ◽

Qiu-Ping Qin ◽

Tri H. Nguyen ◽

...

Keyword(s):

Down Syndrome ◽

Basic Protein ◽

Protein A ◽

Serum Marker ◽

Maternal Serum ◽

Major Basic Protein ◽

Eosinophil Major Basic Protein

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The proform of eosinophil major basic protein: a new maternal serum marker for adverse pregnancy outcome

Prenatal Diagnosis ◽

10.1002/pd.2331 ◽

2009 ◽

Vol 29 (11) ◽

pp. 1013-1019 ◽

Cited By ~ 6

Author(s):

Kasper Pihl ◽

Torben Larsen ◽

Steen Rasmussen ◽

Lone Krebs ◽

Michael Christiansen

Keyword(s):

Pregnancy Outcome ◽

Basic Protein ◽

Adverse Pregnancy Outcome ◽

Protein A ◽

Serum Marker ◽

Maternal Serum ◽

Major Basic Protein ◽

Adverse Pregnancy ◽

Eosinophil Major Basic Protein

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Quantification of Proteolytically Active Pregnancy-Associated Plasma Protein-A with an Assay Based on Quenched Fluorescence

Clinical Chemistry ◽

10.1373/clinchem.2006.080614 ◽

2007 ◽

Vol 53 (5) ◽

pp. 947-954 ◽

Cited By ~ 20

Author(s):

Claus Gyrup ◽

Michael Christiansen ◽

Claus Oxvig

Keyword(s):

Proteolytic Activity ◽

Plasma Protein ◽

Basic Protein ◽

Biological Function ◽

Limit Of Detection ◽

Protein A ◽

Maternal Serum ◽

Serum Samples ◽

A Subunit ◽

Eosinophil Major Basic Protein

Abstract Background: Maternal serum concentrations of pregnancy-associated plasma protein-A (PAPP-A, pappalysin-1, EC 3.4.24.79) are used to predict the occurrence of Down syndrome. In pregnancy, PAPP-A primarily circulates as a covalent 2:2 complex with the proform of eosinophil major basic protein (proMBP), which inhibits the proteolytic activity of PAPP-A. At term, however, ∼1% of PAPP-A exists as an active, uncomplexed dimer with proteolytic activity directed specifically toward insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5. No assays have been developed that allow quantification of PAPP-A proteolytic activity. Methods: We developed a sensitive and specific immunocapture assay for PAPP-A activity based on intramolecular quenched fluorescence. We used a 26-residue synthetic peptide derived from IGFBP-4 in which specific positions on each side of the PAPP-A cleavage site were substituted with 3-nitrotyrosine and o-aminobenzoic acid. Results: The assay detected the activity of recombinant PAPP-A as well as PAPP-A in serum samples from pregnant women. The limit of detection (mean signal of blank plus 3 SD) of the active PAPP-A subunit was 13 pmol/L, and the intra- and interassay CVs were <10% and <15%, respectively. Interestingly, the fraction of active PAPP-A decreased gradually from week 7 to week 19 of pregnancy. Conclusions: This method allows the measurement of PAPP-A enzymatic activity and because of its specificity it is relevant to the study of the biological function of PAPP-A. The method may also be useful in the diagnosis of pregnancy disorders.

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The Effect of Purified Human Eosinophil Major Basic Protein on Mammalian Ciliary Activity1–3

American Review of Respiratory Disease ◽

10.1164/arrd.1987.135.4.848 ◽

1987 ◽

Vol 135 (4) ◽

pp. 848-853 ◽

Cited By ~ 79

Author(s):

Annette T. Hastie ◽

David A. Loegering ◽

Gerald J. Gleich ◽

Friedrich Kueppers

Keyword(s):

Basic Protein ◽

Major Basic Protein ◽

Human Eosinophil ◽

Eosinophil Major Basic Protein

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Localization of eosinophils to airway nerves and effect on neuronal M2 muscarinic receptor function

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1997.273.1.l93 ◽

1997 ◽

Vol 273 (1) ◽

pp. L93-L103 ◽

Cited By ~ 34

Author(s):

R. W. Costello ◽

B. H. Schofield ◽

G. M. Kephart ◽

G. J. Gleich ◽

D. B. Jacoby ◽

...

Keyword(s):

Guinea Pigs ◽

Acetylcholine Release ◽

Basic Protein ◽

Receptor Function ◽

Major Basic Protein ◽

Parasympathetic Nerves ◽

M2 Muscarinic Receptor ◽

Fatal Asthma ◽

Eosinophil Major Basic Protein ◽

M2 Muscarinic Receptors

Neuronal M2 muscarinic receptors inhibit acetylcholine release from pulmonary parasympathetic nerves but are dysfunctional in antigen-challenged animals and asthmatics. Deletion of pulmonary eosinophils protects M2 receptor function in antigen-challenged guinea pigs. Therefore, the association of eosinophils with airway nerves was investigated. Nerve-associated eosinophils were significantly increased in challenged animals compared with controls (0.75 +/- 0.05 vs. 0.28 +/- 0.05 eosinophils/nerve). In antigen-challenged animals, eosinophil density was greatest around airway nerves, suggesting recruitment to the nerves. M2 receptor function was inversely correlated with the number of eosinophils per nerve, thus eosinophils are associated with airway nerves in antigen-challenged guinea pigs, where they impair M2 receptor function. In airways from three patients with fatal asthma, 196 of 637 eosinophils (30%) were associated with nerves, and release of eosinophil major basic protein was evident; conversely, in three control patients 1 of 11 (9%) eosinophils were in contact with nerves. Thus eosinophils and their granule proteins are also seen in association with airway nerves in patients with asthma.

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