The fetus and newborn infant are highly susceptible to infection by pathogens that are capable of intracellular survival. The invasion of these microbes usually stimulates a granulomatous host defense response in the fetus or neonate. Multinucleated giant cells (MGC) are the predominant cells composing the granuloma and represent the terminally differentiated state of activated macrophages. Because macrophages derived from human umbilical cord blood monocytes demonstrate some deficiencies in activated functions, we tested the ability of these cells to form MGC in vitro. Mononuclear cells from umbilical cord blood and adult peripheral blood were isolated and cultured for 7, 14, or 21 d before stimulation with phorbol myristate acetate (PMA), an agent known to stimulate MGC from mononuclear phagocytes in vitro. Spontaneous MGC formation occurred in both cord and adult blood mononuclear cell cultures by d 7 of incubation, although significantly fewer MGC formed in the cord blood cultures. PMA treatment of adult blood mononuclear cells resulted in a significant increase in MGC formation after 7, 14, or 21 d of culture, but PMA did not significantly increase MGC formation in cord blood cultures until 14 or 21 d of culture. Pretreatment of cord and adult blood mononuclear cells with 1,25-dihydroxyvitamin D3 inhibited PMA-in-duced MGC formation. However, when a purified population of cord blood, monocyte-derived macrophages were pretreated with 1,25-dihydroxyvitamin D3, PMA significantly increased MGC formation. These data indicate that distinct differences exist between mononuclear phagocytes isolated from cord blood versus adult peripheral blood with respect to in vitro MGC formation and that a unique population of 1,25-dihydroxyvitamin D3-responsive macrophages is derived from cord blood monocytes.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health