Evidence that polymorphonuclear neutrophils infiltrate into the developing corpus luteum and promote angiogenesis with i
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RESEARCH
Open Access
Evidence that polymorphonuclear neutrophils infiltrate into the developing corpus luteum and promote angiogenesis with interleukin-8 in the cow Sineenard Jiemtaweeboon1, Koumei Shirasuna1*, Akane Nitta1, Ayumi Kobayashi1, Hans-Joachim Schuberth2, Takashi Shimizu1 and Akio Miyamoto1
Abstract Background: After 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 Results: Polymorphonuclear 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. Conclusion: PMNs 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.
Background The corpus luteum (CL) is a unique endocrine organ that develops from the ovulated follicle during the sexual cycle. The main function of the CL is to secrete a large amount of progesterone (P), which is essential for establishment and maintenance of pregnancy. After ovulation, inadequate function of the CL is one of major causes of infertility in cows [1]. Angiogenesis is fundamental to the normal development of the CL in many species. One of the major angiogenic factors, basic fibroblast growth factor (FGF2), is generally involved in cell * Correspondence: [email protected] 1 Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan Full list of author information is available at the end of the article
growth, differentiation, transformation and angiogenesis. Gospodarowizc et al. [2] have been shown that FGF2 is produced in the bovine CL and stimulates neovascularization and proliferation of a wide variety of cells, such as vascular smooth muscle cells, granulosa cells and endothelial cells. Additionally, vascular
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