Evidence that polymorphonuclear neutrophils infiltrate into the developing corpus luteum and promote angiogenesis with interleukin-8 in the cow

Sineenard Jiemtaweeboon,Hans-Joachim Schuberth,Akio Miyamoto,Ayumi Kobayashi,Takashi Shimizu,Koumei Shirasuna,Akane Nitta

doi:10.1186/1477-7827-9-79

Sineenard Jiemtaweeboon, Hans-Joachim Schuberth + Show 5 more

Open Access

https://doi.org/10.1186/1477-7827-9-79

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Abstract

BackgroundAfter ovulation in the cow, the corpus luteum (CL) rapidly develops within a few days with angiogenesis and progesterone production. CL formation resembles an inflammatory response due to the influx of immune cells. Neutrophils play a role in host defense and inflammation, and secrete chemoattractants to stimulate angiogenesis. We therefore hypothesized that neutrophils infiltrate in the developing CL from just after ovulation and may play a role in angiogenesis of the CL.Methods and ResultsPolymorphonuclear neutrophils (PMN) were detected in CL tissue by Pas-staining, and interleukin-8 (IL-8, a neutrophil-specific chemoattractant) was measured in supernatant of the CL tissue culture: considerable amounts of PMNs and the high level of IL-8 were observed during the early luteal phase (days 1-4 of the estrous cycle). PMNs and IL-8 were low levels in the mid and late luteal phases, but IL-8 was increased during luteal regression. The PMN migration in vitro was stimulated by the supernatant from the early CL but not from the mid CL, and this activity was inhibited by neutralizing with an anti-IL-8 antibody, indicating the major role of IL-8 in inducing active PMN migration in the early CL. Moreover, IL-8 stimulated proliferation of CL-derived endothelial cells (LECs), and both the supernatant of activated PMNs and IL-8 stimulated formation of capillary-like structures of LECs.ConclusionPMNs migrate into the early CL partially due to its major chemoattractant IL-8 produced at high levels in the CL, and PMNs is a potential regulator of angiogenesis together with IL-8 in developing CL in the cow.

Highlights

After ovulation in the cow, the corpus luteum (CL) rapidly develops within a few days with angiogenesis and progesterone production
polymorphonuclear neutrophils (PMN) migrate into the early CL partially due to its major chemoattractant IL-8 produced at high levels in the CL, and PMNs is a potential regulator of angiogenesis together with IL-8 in developing CL in the cow
Luteal cells (LCs) was isolated from the bovine mid CL (Days 8-12 of the estrous cycle) using magnetic tosylactivated beads coating with BS-1 lectin, BS-1 negative cells were assessed as enriched LCs as described previously [25]

Summary

Introduction

After ovulation in the cow, the corpus luteum (CL) rapidly develops within a few days with angiogenesis and progesterone production. We hypothesized that neutrophils infiltrate in the developing CL from just after ovulation and may play a role in angiogenesis of the CL. One of the major angiogenic factors, basic fibroblast growth factor (FGF2), is generally involved in cell Cytokines and chemokines, such as prostaglandins (PGs) [4], tumor necrosis factor a (TNFa) [5], interleukin (IL)-1 [6] and IL-8 [7,8] are found in high concentrations in the follicular fluid in the pre-ovulatory phase. A multitude of leukocytes, such as macrophages and eosinophils are located in the luteinizing theca area in the developing CL [11,12,13] This series of phenomena from ovulation to luteal development involves bleeding, immune cell infiltration, tissue remodeling and angiogenesis, implying that the development of the CL following ovulation is a kind of physiological injury with an inflammatory response. PMNs secrete VEGFA [14] and induce the sprouting of capillary-like structures of endothelial cells in vitro [15], suggesting that PMNs have a potential role, in phagocytosis, and in the regulation of angiogenesis

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