Ninjurin1 mediates macrophage-induced programmed cell death during early ocular development.

Developmental tissues go through regression, remodeling, and apoptosis. In these processes, macrophages phagocytize dead cells and induce apoptosis directly. In hyaloid vascular system (HVS), macrophages induce apoptosis of vascular endothelial cells (VECs) by cooperation between the Wnt and angiopoietin (Ang) pathways through cell-cell interaction. However, it remains unclear how macrophages are activated and interact with VECs. Here we show that Ninjurin1 (nerve injury-induced protein; Ninj1) was temporally increased in macrophages during regression of HVS and these Ninj1-expressing macrophages closely interacted with hyaloid VECs. Systemic neutralization using an anti-Ninj1 antibody resulted in the delay of HVS regression in vivo. We also found that Ninj1 increased cell-cell and cell-matrix adhesion of macrophages. Furthermore, Ninj1 stimulated the expression of Wnt7b in macrophages and the conditioned media from Ninj1-overexpressing macrophages (Ninj1-CM) decreased Ang1 and increased Ang2 in pericytes, which consequently switched hyaloid VEC fate from survival to death. Collectively, these findings suggest that macrophages express Ninj1 to increase the death signal through cell-cell interaction and raise the possibility that Ninj1 may act similarly in other developmental regression mediated by macrophages.

Hormonal effects of the 300 microgram norethisterone (NET) minipill. 2. Daily gonadotrophin levels in 43 subjects during a pretreatment cycle and during the second month of NET administration.

PIP: This is the second of 2 articles studying the ovarian reaction of 43 women to daily administration of 300 mg of norethisterone (NET) minipill. The present article deals with the assessment of daily changes in immunoreactive follicle stimulating hormone (FSH) and luteinizing hormone, (LH) during the pretreatment cycle, and during the second month of administration. In 29 of the 43 subjects LH levels were also analyzed in vitro by a bioassay procedure. Administration of NET minipill did not influence the mean FSH and LH levels during days 4-6 of the cycle, but suppressed the FSH peak value in all patients. On the other hand there were significant differences in the LH levels of the pretreatment cycles. In the majority of women with ovulatory estradiol and progesterone level, the preovulatory FSH and LH peaks were below the normal value. It seemed apparent that ovarian suppression by the NET minipill was not related to the inhibition of FSH and LH secretion as reflected by their peripheral levels.^ieng