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B. X. Pan, J. E. Schechter, C. Ding, A. K. Mircheff; Evidence for Interactions Between Environmental Adverseness and the Hormonal Milieu of Pregnancy in Promoting Formation of Atypical, Prolactin Immunopositive, Periacinar Lymphocyte Aggregates. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4186.
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Previous studies have established that both external environment and systemic hormone levels influence mediator expression and immunoarchitecture in the lacrimal glands (LG) of female rabbits. When environmental conditions are adverse to the ocular surface, lymphocytes accumulate in aggregates predominantly around venules and interlobular ducts. Late in pregnancy, when serum prolactin (PRL) levels are elevated, PRL immunoreactivity (IR) accumulates in both acinar and interlobular duct epithelial cells, and lymphocytes and plasmacytes redistribute from perivenular/periductal sites to the interacinar stroma. We have now studied a group of pregnant rabbits that had been exposed to a dry environment that promoted increased expression of both proinflammatory (IL-1a, IL-1b, IL-2) and regulatory (IL-4 , IL-10) cytokines and increased lymphocytic infiltration in non-pregnant animals.
Six pregnant and 6 non-pregnant female control rabbits were raised in an outdoor environment with daily humidity < 20% for 30 days. mRNA was extracted from whole LG and processed for real time RT-PCR. Cryosections were processed for IHC with standard protocol.
ANOVA and multiple comparison revealed that PRL mRNA abundance in 7 LGs from pregnant rabbits (median 5.9 x 10-4) did not differ significantly from LGs of non-pregnant rabbits (median 4.1 x 10-3). However, it was markedly greater in 5 glands from pregnant rabbits (median 1.7 x 10-2). Among all 12 glands, the abundances of mRNAs for IL-2, IL-4, IL-6, IL10, CCL2, CCL4, CCL21, CD28 correlated strongly (p > 0.83) and significantly (P < 9.2 x10-4) with the abundance of PRL mRNA. PRL IR levels in interlobular duct epithelial cells did not differ markedly between the glands with low and high PRL mRNA abundances. However, increasing abundance of PRL mRNA was associated with increasing PRL IR in the stroma near the acini, where it was associated with small clusters of immunoreactive lymphocytes. Such clusters were infrequent in glands with low PRL mRNA abundance.
Findings are consistent with the hypotheses that: (a) Increased interlobular duct cell PRL IR during pregnancy reflects increased uptake, storage, and recycling of PRL from the circulation. (b) Environmental conditions that are adverse to the ocular surface interact with the systemic hormonal milieu of pregnancy to promote the formation of atypical, PRL expressing lymphocyte aggregates in the periductal stroma.
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