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Decidual macrophages: key regulators of vascular remodeling in human pregnancy

Lookup NU author(s): Dr Gendie Lash, Hedele Pitman, Barbara Innes, Dr Judith Bulmer

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Abstract

Successful remodeling of the uterine spiral arteries is essential for a complication-free pregnancy and is best described in terms of its morphologic features. The molecular mediators and cellular sources of spiral artery remodeling are not known, although a role for uterine leukocytes has been proposed. Immunohistochemical assessment of placental bed biopsies demonstrated uterine NK cells, macrophages, and T lymphocytes in the wall and adventitia of spiral arteries at different stages of remodeling, regardless of the presence of extravillous trophoblast cells. Leukocytes were more prevalent in vessel adventitia than wall, and macrophages were the most abundant leukocyte population. Macrophages, separated from early pregnancy decidua, did not alter extravillous trophoblast cells invasion or vascular smooth muscle cell organization or differentiation status but did induce extracellular matrix breakdown (reduced immunostaining of laminin, P = 0.05; fibronectin, P = 0.02) andwere able to phagocytose apoptotic vascular smooth muscle cells. Decidual macrophages were shown to secrete a wide range of cytokines (IL-1 beta, -2, -4, -5, -6, -8, -10, and -13 and TNF-alpha), proteases (matrix metalloproteinase-1, -2, -7, -9, and -10), and angiogenic growth factors (angiogenin, keratinocyte growth factor, fibroblast growth factor B, vascular endothelial growth factor A, and angiopoietin-1 and -2). We conclude that spiral artery remodeling involves the coordinated activity of a range of cell types, including extravillous trophoblast cells, decidual uterine NK cells, and macrophages in a carefully, spatiotemporally regulated manner.

Publication metadata

Author(s): Lash GE, Pitman H, Morgan HL, Innes BA, Agwu CN, Bulmer JN

Publication type: Article

Publication status: Published

Journal: Journal of Leukocyte Biology

Year: 2016

Volume: 100

Issue: 2

Pages: 315-325

Print publication date: 01/08/2016

Online publication date: 27/01/2016

Acceptance date: 11/01/2016

ISSN (print): 0741-5400

ISSN (electronic): 1938-3673

Publisher: Federation of American Societies for Experimental Biology

URL: http://dx.doi.org/10.1189/jlb.1A0815-351R

DOI: 10.1189/jlb.1A0815-351R

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