Immunocytochemical Studies of Adhesion Molecules on Mouse UNK Cells and Their Extracellular Matrix Ligands During Mouse Pregnancy

Abstract

Uterine natural killer (uNK) cells are the dominant lymphocytes of pregnant mammals' uterus. Studies have identified four differentiation stage of mouse uNK cells based on Dolichos biflorus lectin cytochemistry, and their distribution showed preferential domain in the uterus through out the pregnancy. This work was done to investigate the expression of alpha5, alpha6, and beta7 integrins on uNK cells and their ligands distribution. Section of mouse uterus from sixth to seventeenth gestational days were submitted to immunocytochemistry and positive reactions for alpha5, alpha6, and beta7 integrins were found on uNK from eighth to tenth gestational days but not after twelfth gestational days. Fibronectin reactions were seemed from sixth to tenth gestational days around uNK from the myometrium and endometrium close to the myometrium. No reaction for fibronectin was seen in the decidualized and nondecidualized endometrium near the placenta. Laminin reaction was seen just in the antimesometrial side. beta7 integrin seems to be the active receptor to bind with VCAM-1 or MAdCAM-1 of endothelial cells, promoting the uNK cross through the vessels. The absence of laminin in an uNK domain suggests these cells are not dependent of laminin and alpha6 integrin for their establishment. However, fibronectin seems to support uNK migration, proliferation, differentiation, and survival in the uterus by binding with alpha5 integrin. The loss of alpha5 integrin ligation by the down regulation of fibronectin could inhibits these events and further studies are need to investigate whether unligated alpha5 can actively and initiate apoptosis, maybe in a caspase 8-dependent way that has been called integrin-mediated death.

Leukocyte driven-decidual angiogenesis in early pregnancy

“…Individual expression of ITGA4 or ITGA7 is described in uNK cells at this gestational interval. 75,76 Interactions of chemokines expressed by decidual cells and their receptors on leukocytes also regulate leukocyte entrance to decidua basalis. Chemokines involved in leukocyte recruitment into mouse decidua basalis are still largely unknown.…”

Extracellular matrix in epitheliochorial, endotheliochorial and haemochorial placentation and its potential application for regenerative medicine

“…Type IV collagen contributes to the development and maintenance of the ECM, because it fixes other basement membrane components, for example laminin, entactin and heparin sulfate proteoglycan (Bryant‐Greenwood, ). In rats and mice, collagen fibres are found near the implantation sites and also in the intercellular spaces of the developing placenta (Welsh & Enders, ; Zavan, Paffaro, Joazeiro, Yamada, & Paffaro, ). Decorin seems to play an important role for uterine collagen fibrillogenesis.…”

Expressão do complexo receptor CD74 - CD44 para o fator de inibição de migração de macrófagos (MIF) na interface materno placentária em camundongos.

“…Ao redor do 13º dia de gestação esta estrutura já se encontra reduzida e quase vestigial (Katz e Abrahamsohn, 1987). A região de células decidualizadas passa a ser ocupada pela expansão da glândula metrial, tecido endometrial mais distal em relação ao embrião e que abriga células imunologicamente competentes entre as quais se destacam as células natural killer uterinas (Paffaro et al, 2003;Zavan et al, 2010). Estas células têm função primordial na gestação, uma vez que se acredita que limitam a invasão das células trofoblásticas (Kiso et al, 1992) por meio da sua atividade citotóxica (Manaseki e Searle, 1989) e produção de interferon gama (Marzusch et al, 1997) e ainda, suportam o desenvolvimento normal da decídua e vasculatura uterina via cascatas de sinalização envolvendo tradução de sinal mediada por interleucina-12 (Croy et al,1997a).…”

“…Neste estudo, os subtipos de leucócitos CD74 e CD44 reativos não foram caracterizados, mas é possível que pelo menos parte dos leucócitos endovasculares e outros presentes na decídua pertençam à população de células NK, uma vez que estas células são abundantes na decídua mesometrial (Paffaro et al, 2003;Zavan et al, 2010). Coerente com esta possibilidade, Hannan et al (2010) sugeriram em humanos, que macrófagos e células NK uterinas durante a gestação expressam altos níveis de transcritos e moléculas de CD44 na superfície celular.…”