Defective macrophage recruitment and clearance of apoptotic cells in the uterus of osteopetrotic mutant mice lacking macrophage colony-stimulating factor (M-CSF).
There are large numbers of macrophages in the uterus of normal mice. During estrus and metestrus endometrial epithelial cells express macrophage colony-stimulating factor (M-CSF). Numbers of uterine macrophages showed cyclic changes and accumulated beneath the endometrial epithelial cells at estrus and metestrus. However, numbers of uterine macrophages in osteopetrotic (op/op) mice were reduced tenfold compared with normal littermate mice and op/op mouse macrophages were ultrastructurally immature throughout the estrous cycle. Several macrophage chemokines were produced in the uterus. However, administration of antibody against the macrophage colony stimulating factor receptor (c-fms) severely diminished the number of uterine macrophages in normal littermate mice, implying that M-CSF plays a major role in macrophage recruitment in the uterus. Endometrial epithelial cells underwent apoptosis at estrus and metestrus and were disposed into the uterine lumen in op/op mice and littermate mice. In littermate mice a large number of macrophages accumulated beneath the endometrial epithelial cells and actively removed apoptotic cells. In contrast, there were few macrophages in op/op mice and clearance of apoptotic cells by macrophages was defective in the uterus of these mice. Thus M-CSF plays important roles in the recruitment and differentiation of macrophages and in scavenging effete epithelial cells in the uterus.
Shimada-Hiratsuka
M
M
Second Department of Pathology, Niigata University School of Medicine, Japan.
Naito
M
M
Kaizu
C
C
Shuying
J
J
Hasegawa
G
G
Shultz
L D
LD
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008264:Macrophages / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D010022:Osteopetrosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D010587:Phagocytosis / Q000502:physiology; D014599:Uterus / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure
D016173:Macrophage Colony-Stimulating Factor