Evidence of changes in the immunophenotype and metabolic characteristics (intracellular reactive oxygen radicals) of fetal, but not maternal, monocytes and granulocytes in the fetal inflammatory response syndrome.
OBJECTIVE
The fetal inflammatory response syndrome (FIRS) is present in a fraction of fetuses exposed to intra-amniotic infection and is associated with the impending onset of labor and multisystem organ involvement. Neonates born with funisitis, the histologic counterpart of fetal systemic inflammation, are at increased risk for cerebral palsy and bronchopulmonary dysplasia. The aim of this study was to determine whether fetal and maternal granulocytes and monocytes have the phenotypic and metabolic characteristics of activation in cases with FIRS.


METHODS
A case-control study was conducted with umbilical cord and maternal blood samples obtained from patients who delivered preterm with (n=30) and without funisitis (n=15). The phenotypic characteristics of granulocytes and monocytes were examined using flow cytometry and monoclonal antibodies including CD11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Intracellular reactive oxygen species (iROS) were measured at the basal state and after stimulation (oxidative burst). A P<0.01 was considered statistically significant.


RESULTS
(1) Funisitis was associated with a significant increase in the median mean channel brightness (MCB) of CD14, CD64, and CD66b on granulocytes and the MCB of CD64 on monocytes collected from umbilical cord blood. (2) The basal iROS production and oxidative burst were higher in the umbilical cord monocytes of neonates with funisitis than in those without funisitis. (3) There were no differences in the immunophenotype, basal iROS production, and oxidative burst in maternal granulocytes or monocytes between the study groups.


CONCLUSIONS
Fetal systemic inflammation is associated with phenotypic and metabolic changes consistent with activation in fetal immune cells but not in maternal blood.
Kim
Sun Kwon
SK
Perinatology Research Branch, NICHD, NIH, DHHS, Wayne State University/Hutzel Women's Hospital, Detroit, MI 48201, USA.
Romero
Roberto
R
Chaiworapongsa
Tinnakorn
T
Kusanovic
Juan Pedro
JP
Mazaki-Tovi
Shali
S
Mittal
Pooja
P
Erez
Offer
O
Vaisbuch
Edi
E
Gotsch
Francesca
F
Pacora
Percy
P
Yeo
Lami
L
Gervasi
Maria Teresa
MT
Lamont
Ronald F
RF
Yoon
Bo Hyun
BH
Hassan
Sonia S
SS
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D016022:Case-Control Studies; D002821:Chorioamnionitis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005312:Fetal Blood / Q000276:immunology / Q000378:metabolism; D006098:Granulocytes / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D007231:Infant, Newborn; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D014470:Umbilical Cord / Q000473:pathology; D055815:Young Adult
D015703:Antigens, CD; D017382:Reactive Oxygen Species