Premium
Upregulation and release of soluble fms‐like tyrosine kinase receptor 1 mediated by complement activation in human syncytiotrophoblast cells
Author(s) -
Banadakoppa Manu,
Balakrishnan Meena,
Yallampalli Chandra
Publication year - 2018
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.13033
Subject(s) - downregulation and upregulation , syncytiotrophoblast , trophoblast , complement system , secretion , microbiology and biotechnology , receptor , anaphylatoxin , biology , endocrinology , chemistry , immunology , placenta , antibody , biochemistry , fetus , gene , pregnancy , genetics
Problem Antiangiogenic molecule soluble fms‐like tyrosine kinase receptor 1 ( sFLT 1) released from trophoblast cells is associated with pregnancy‐specific hypertensive disorder pre‐eclampsia. Cause of elevated sFLT 1 in pre‐eclampsia patients is not well understood. Despite evidence of excess systemic and placental complement activation in pre‐eclampsia patients, its role in pathophysiology is not clear. If the complement activation plays a role in upregulation and secretion of sFLT 1 is not known. Method of study Human trophoblast cells were isolated from term placentas and allowed to syncytialize. Complement was activated in vitro at sublethal levels on syncytiotrophoblast cells. Effect of complement activation on expression and release of sFLT 1 was assessed by comparing its levels in these cells with and without complement activation. Results Sublethal level of complement activation on syncytialized human trophoblast cells induced upregulation of sFLT 1 mRNA and protein. Complement also induced secretion of sFLT 1 in a manner depending on degree of activation. Anaphylatoxins C3a induced upregulation but not the release of sFLT 1. Release of terminal membrane attack complex ( MAC ) was associated with sFLT 1 secretion. Conclusion Complement activation plays a major role in both the expression and secretion of sFLT 1 from syncytial trophoblast cells. The terminal MAC complex is involved in its secretion. Increased levels of sFLT 1 in pre‐eclampsia patients may be due to complement‐induced upregulation and secretion.