Angiotensin II increases sperm phagocytosis by neutrophils in vitro: A possible physiological role in the bovine oviduct.

This study aimed to investigate the possible effects of the vasoactive peptide angiotensin II (ANG II), secreted by bovine oviduct epithelial cells, on the in vitro phagocytic activity of polymorphonuclear leukocytes, specifically neutrophils, towards sperm. The measured concentrations of ANG II in oviduct flushes and conditioned medium from primary bovine oviduct epithelial culture ranged from 10(-10) to 10(-11)  M. In our experiments, neutrophils were incubated for 2 hr with ANG II (0, 10(-11) , 10(-10) , 10(-9) , and 10(-8)  M). Phagocytosis and superoxide production were then assessed by co-incubation of these neutrophils with sperm pretreated to induce capacitation, revealing a dose-dependent increase in both metrics by ANG II. This stimulatory effect of ANG II was eliminated by losartan, an angiotensin receptor type 1 (AGTR1) antagonist. ANG II also suppressed neutrophil transcription of angiotensin converting enzyme-1 (ACE) and AGTR1, but not AGTR2, suggesting the involvement of the AGTR1 receptor-mediated pathway in the response to sperm. Scanning electron microscopy further revealed that incubation of neutrophils with ANG II stimulated the formation of DNA-based extracellular traps for sperm entanglement. The addition of prostaglandin E2 at concentrations found in the oviduct suppressed the ANG II-stimulated phagocytic activity of neutrophils towards sperm. Thus the physiological levels of ANG II stimulate neutrophil phagocytosis of sperm in vitro, and suggest that an angiotensin/prostaglandin E2 system may fine-tune the local immune response that fosters sperm survival in the bovine oviduct. Mol. Reprod. Dev. 83: 630-639, 2016. © 2016 Wiley Periodicals, Inc.