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Is Produced by Polymorphonuclear Neutrophils in Human Uterine Endometrium and by Cultured Peripheral Blood Polymorphonuclear Neutrophils1
Departments of
*
Microbiology and
Physiology, Dartmouth Medical School, Lebanon, NH 03756
Cytokines present in the human uterus play an important role both
in modulating immune responses to infectious challenge and in the
establishment and maintenance of pregnancy. In particular, successful
implantation and pregnancy is thought to require the establishment of a
Th2 environment, while Th1 cytokines are associated with pregnancy loss
and infertility. On the other hand, a Th1 response appears to be
required for the resolution of acute infection. Using novel confocal
microscopic analysis of fresh sections of human tissue, we have
investigated the production of IFN-
, a Th1 cytokine, in human
endometria. Extracellular IFN-, mostly associated with matrix
components, was located immediately beneath the luminal epithelium and
along the glandular epithelium proximal to the lumen. As evidenced by
intracellular staining, IFN- is produced by both stromal cells and
intraepithelial lymphocytes through all stages of the menstrual cycle.
Surprisingly, the stromal cell containing intracellular IFN- was
identified as a polymorphonuclear neutrophil on the basis of its
reactivity with a panel of mAbs and its nuclear morphology. We further
found that polymorphonuclear neutrophils isolated from normal donors
produce IFN- in response to stimulation with LPS, IL-12, and
TNF-
. Taken together, these findings suggest that polymorphonuclear
neutrophils are capable of producing IFN- both in vitro and in vivo,
indicating that their role in shaping immune responses may be more
extensive than previously thought. Furthermore, these studies strongly
suggest that polymorphonuclear neutrophils play an important role in
determining immune responsiveness within the female reproductive tract.
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