Neutrophil recruitment and function in endometriosis patients and a syngeneic murine model

Lindsey K Symons, Jessica E Miller, Kathrin Tyryshkin, Stephany P Monsanto, Ryan M Marks, Harshavardhan Lingegowda, Kaitlin Vanderbeck, Timothy Childs, Steven L Young, Bruce A Lessey, Madhuri Koti, Chandrakant Tayade
FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019 · vol. 34(1) , pp. 1558–1575 · doi:10.1096/fj.201902272r · PMID:31914688 · W2992652511
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Abstract

Endometriosis is a chronic inflammatory, gynecological disease characterized by the presence of endometrial-like tissue lesions outside of the uterus. Neutrophils are elevated in the systemic circulation and peritoneal fluid of endometriosis patients; however, whether and how neutrophils contribute to endometriosis pathophysiology remain poorly understood. With emerging roles for neutrophils in chronic and sterile inflammatory conditions, we sought to provide in-depth characterization of neutrophil involvement in endometriosis. We demonstrate that neutrophils reside within patient endometriotic lesions and that patient lesions possess a microenvironment that may influence neutrophil recruitment and function. We also provide the first evidence that systemic circulating neutrophils from endometriosis patients display distinct transcriptomic differences compared neutrophils from healthy control subjects. Time course characterization of our syngeneic, immunocompetent mouse model of endometriosis revealed that neutrophils are rapidly recruited to the peritoneal environment early after endometriotic lesion establishment and remain present in murine lesions long term. In vivo neutrophil depletion altered the systemic and peritoneal immune microenvironment of mice with endometriosis as demonstrated by changes in pro-inflammatory and angiogenic mediators. Taken together, these findings highlight a novel role for neutrophils in early events such as angiogenesis and modulation of the local inflammatory environment associated with endometriosis pathogenesis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Neutrophils Animals Disease Models, Animal Endometriosis Endometrium Female Humans Inflammation Inflammation Mice Neovascularization, Pathologic Neovascularization, Pathologic Neutrophil Infiltration Neutrophil Infiltration Neutrophils Peritoneum Peritoneum

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