Prior studies have shown that the eosinophil granule contains an intensely cationic proteinaceous molecule termed the major basic protein (gMBP). Guinea pig MBP accounts for over 50% of granule proteins and 25% of the total cellular protein. gMBP is localized to the core of the granule and exists there as a crystal. gMBP has also been identified in the human; both guinea pig and human gMBP are potent toxins to helminths and mammalian cells; and gMBP has been proposed as a mediator of pathological damage in bronchial asthma and other inflammatory diseases. During studies of the role of gMBP in hypersensitivity diseases, we found that elevated levels of gMBP are present in human pregnancy. MBP levels rise shortly after conception, plateau at about 20 weeks and show a late rise shortly before labor. The pregnancy-associated major basic protein (pMBP) behaves identically to gMBP in its immunochemical properties, but initial studies showed a difference in molecular weight. In recent studies, we have found that a late rise in pMBP levels is associated with human labor. In this proposal, we outline studies, first, to purify pMBP from placenta in quantities sufficient for chemical analyses. Second, we will test whether purified pMBP is identical to gMBP. These experiments are predicted on our ability to purify pMBP and on prior physicochemical information concerning gMBP. Third, we will measure levels of serum pMBP throughout human pregnancy in 100 normal pregnant women and in a control group of 30 nonpregnant women. And fourth, we will measure serum pMBP levels in various pathological conditions associated with pregnancy, including tests of the hypothesis that elevations of pMBP before 36 weeks predict premature labor. We also will test whether pMBP is useful in the management of prolonged pregnancy and whether a subset of patients with recurrent abortions may have abnormalities in the plasma levels of pMBP. Overall, these experiments will determine whether spontaneous labor can be predicted by late rises in pMBP and they offer the hope of obtaining new information concerning the function in human pregnancy of the relatively neglected trophoblast known as the X cell.
Showing the most recent 10 out of 11 publications
