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1 June 2017 Changes in immune cell distribution and their cytokine/chemokine production during regression of the rhesus macaque corpus luteum
Cecily V. Bishop, Fuhua Xu, Rosemary Steinbach, Ellie Ficco, Jeffrey Hyzer, Steven Blue, Richard L. Stouffer, Jon D. Hennebold
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Abstract

Our previous flow cytometry results demonstrated a significant increase in neutrophils, macrophages/monocytes, and natural killer (NK) cells in dispersed rhesus monkey corpora lutea (CL) after progesterone (P4) levels had fallen below 0.3 ng/ml for ≥3 days during the natural menstrual cycle. In this study, immunohistochemistry revealed the CD11b+ cells (neutrophils, macrophages/monocytes) present in the CL after luteal P4 synthesis ceased were distributed throughout the tissue. CD16+ cells (presumptive NK cells) were observed mainly near the vasculature in functional CL, until their numbers increased and they became widely distributed in regressing CL. To determine if the immune cells that enter luteal tissue during structural regression are functionally different from those that are present during peak function, CD11b+ or CD16+ populations were enriched from mid-late stage (functional) and regressing (days 1.8 ± 0.3 postmenses) CL using antibody-conjugated magnetic microbeads. Flow cytometry analyses revealed the majority of CD11b+ cells expressed CD14, a protein mainly produced by macrophages/monocytes. The antibody-enriched and depleted fractions were cultured for 24 h, and the media then analyzed for the production of 29 cytokines/chemokines. From the mid-late CL, the CD11b+-enriched fraction produced three cytokines/chemokines, whereas CD16+-enriched cells only produced the chemokine CCL2. However, CD11b +-enriched cells isolated from regressed CL produced eight cytokines/chemokines. The CD16+-enriched cells isolated from regressing CL produced significant levels of only three cytokines. Thus, the CD11b+ cells that appear in the rhesus macaque CL after functional regression produce several cytokines/chemokines that likely play a role in orchestrating structural regression.

Summary Sentence

Cessation of progesterone synthesis at the end of the menstrual cycle leads to increases in monocytes/macrophage and neutrophil numbers, as well as in the type and level of the chemokines and cytokines they secrete.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Cecily V. Bishop, Fuhua Xu, Rosemary Steinbach, Ellie Ficco, Jeffrey Hyzer, Steven Blue, Richard L. Stouffer, and Jon D. Hennebold "Changes in immune cell distribution and their cytokine/chemokine production during regression of the rhesus macaque corpus luteum," Biology of Reproduction 96(6), 1210-1220, (1 June 2017). https://doi.org/10.1093/biolre/iox052
Received: 19 December 2016; Accepted: 30 May 2017; Published: 1 June 2017
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