PRODUCTION AND EXPRESSION OF GRANULOCYTE-COLONY-STIMULATING AND MACROPHAGE-COLONY-STIMULATING FACTORS IN NEWBORNS - THEIR ROLES IN LEUKOCYTOSIS AT BIRTH

We analyzed the production and expression of three colony-stimulating factors (CSFs) in neonates to clarify the mechanism of leukocytosis at birth. Serial blood samples (n = 23) were collected from mothers, cor d blood, and from newborn infants on days 1, 5, and 30 after birth. Th e serum levels of granulocyte-CSF (G-CSF), granulocyte/macrophage-CSF (GM-CSF) and macrophage-CSF (M-CSF) were measured by ELISA. The G-CSF levels on day 1 after birth were significantly higher than those there after, and they were also higher in the mothers than those on days 5 a nd 30 after birth. The GM-CSF levels did not change significantly duri ng the neonatal period. The serum M-CSF levels were higher on postnata l day 1 than at other times, and gradually decreased thereafter. To co nfirm the production sites of G-CSF and M-CSF, the mRNA for these CSFs in peripheral mononuclear cells (MNCs) from healthy adults, mothers, and cord blood were analyzed by PCR. The expression of G-CSF and GM-CS F mRNA was undetectable in MNCs from adults, mothers, and cord blood, while these cells expressed low levels of M-CSF mRNA. After stimulatio n with lipopolysaccharide or phorbol myristate acetate, the MNCs expre ssed high levels of G-CSF and GM-CSF mRNA. The levels of G-CSF PCR pro ducts in cord MNCs were lower than those in adult and maternal MNCs. T he expression of M-CSF mRNA was virtually unchanged by stimulation. To detect the localization of C-CSF and M-CSF in the placenta and umbili cal cord, these tissues were immunocytochemically stained with anti-G- CSF and anti-M-CSF antibodies. G-CSF and M-CSF were expressed in troph oblasts and decidual stromal cells, whereas the umbilical cord did not express these CSFs. Moreover, large amounts of G-CSF and M-CSF were d etected in the supernatant of cultured trophoblasts and decidual strom al cells. The expression of G-CSF and M-CSF in these cells was confirm ed by PCR. These findings suggested that G-CSF and M-CSF produced in t he placenta (trophoblasts and decidual stromal cells) are the major fa ctors that induce leukocytosis in newborn infants at birth.