Production and Expression of Granulocyte- and Macrophage-Colony-Stimulating Factors in Newborns: Their Roles in Leukocytosis at Birth

Abstract

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, cord blood, and from newborn infants on days 1,5, and 30 after birth. The serum levels of granulo-cyte-CSF (G-CSF), granulocyte/macrophage-CSF (GM-CSF) and macro-phage-CSF (M-CSF) were measured by ELISA. The G-CSF levels on day 1 after birth were significantly higher than those thereafter, and they were also higher in the mothers than those on days 5 and 30 after birth. The GM-CSF levels did not change significantly during the neonatal period. The serum M-CSF levels were higher on postnatal day 1 than at other times, and gradually decreased thereafter. To confirm 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-CSF mRNA was undetectable in MNCs from adults, mothers, and cord blood, while these cells expressed low levels of M-CSF mRNA. After stimulation with lipopolysaccharide or phorbol myristate acetate, the MNCs expressed high levels of G-CSF and GM-CSF mRNA. The levels of G-CSF PCR products in cord MNCs were lower than those in adult and maternal MNCs. The expression of M-CSF mRNA was virtually unchanged by stimulation. To detect the localization of G-CSF and M-CSF in the placenta and umbilical cord, these tissues were immunocytochemically stained with anti-G-CSF and anti-M-CSF antibodies. G-CSF and M-CSF were expressed in trophoblasts and decidual stromal cells, whereas the umbilical cord did not express these CSFs. Moreover, large amounts of G-CSF and M-CSF were detected in the supernatant of cultured trophoblasts and decidual stromal cells. The expression of G-CSF and M-CSF in these cells was confirmed by PCR. These findings suggested that G-CSF and M-CSF produced in the placenta (trophoblasts and decidual stromal cells) are the major factors that induce leukocytosis in newborn infants at birth.

Leukocyte Counts in Relation to the Method of Delivery during the First Five Days of Life

“…These effects have been mainly related to endocrine-metabolic variations, particularly the increased cortisol and catecholamine secretion after stressful delivery, or, to a lesser extent, to anesthetic drugs given to the mother during general anesthesia for cesarean section. The increase of neutrophils after stressful delivery may also be related to the displacement of neutrophils from the marginal layer of vessels, which is known to happen after violent exercise in adults [14], or to variations in the production of hematopoietic growth factors, mainly granulocyte colony stimulating factor and granulocyte-macrophage colony stimulation factor [15].…”

Interpretation of automated blood cell counts

“…Son olarak püberte döneminde hormonal deği-şimlere bağlı olarak kızlarda menstrüel kan kaybına bağlı demir eksikliğine eğilim erkeklerde ise yük-sek Hb değerleri görülmektedir [26,27]. Riskli gebeliklere ve doğum stresine bağlı olarak annede artan stres hormonların etkisiyle yenidoğan lökositoz ve nötrofiliye eğilimle doğar [29]. Dört ay-4 yaş arasında geçirilen viral enfeksiyonlar ve sık tekrarlanan aşılamaya bağlı aşı yanıtının etkisi nedeniyle fizyolojik lenfositoz izlenir [28,30].…”

Concentration of Macrophage Colony-Stimulating Factor (M-CSF) in Bovine Peripheral Blood during Pregnancy

“…high concentration of maternal serum M-CSF [9]. Furthermore, it has been reported that low concentrations of serum M-CSF are associated with unexplained recurrent spontaneous abortion in humans [4,14].…”

“…Furthermore, M-CSF concentrations in maternal peripheral blood during the estrous cycle and pregnancy have been reported in humans and mice. In humans, M-CSF concentrations in maternal peripheral blood increase as pregnancy progresses, peak at term and then decrease immediately after parturition until they reach the base level of non-pregnancy [7,9,16,24,28,31,32,34,36]. Ishii et al reported that M-CSF in maternal peripheral blood is produced in the uterus, placenta and peripheral monocytes and that M-CSF of uterine and placental origin is related to a There were no significant differences depending on the stage of the estrous cycle.…”

“…The serum M-CSF level in pregnant women has been found to be higher than that in non-pregnant women [7,16,24,28,31,32,34,36]. In addition, it has been found that the high level of M-CSF in the peripheral blood of pregnant women is caused by M-CSF production in the human placenta [9,11,20] and endometrium [23,36]. These findings suggest that M-CSF plays an important role in human and mouse pregnancy.…”