Characterisation of a novel Fc conjugate of Macrophage Colony-Stimulating Factor (CSF1)

We have produced an Fc conjugate of colony-stimulating factor (CSF) 1 with an improved circulating half-life. CSF1-Fc retained its macrophage growth-promoting activity, and did not induce proinflammatory cytokines in vitro. Treatment with CSF1-Fc did not produce adverse effects in mice or pigs. The impact of CSF1-Fc was examined using the Csf1r-enhanced green fluorescent protein (EGFP) reporter gene in MacGreen mice. Administration of CSF1-Fc to mice drove extensive infiltration of all tissues by Csf1r-EGFP positive macrophages. The main consequence was hepatosplenomegaly, associated with proliferation of hepatocytes. Expression profiles of the liver indicated that infiltrating macrophages produced candidate mediators of hepatocyte proliferation including urokinase, tumor necrosis factor, and interleukin 6. CSF1-Fc also promoted osteoclastogenesis and produced pleiotropic effects on other organ systems, notably the testis, where CSF1-dependent macrophages have been implicated in homeostasis. However, it did not affect other putative CSF1 targets, notably intestine, where Paneth cell numbers and villus architecture were unchanged. CSF1 has therapeutic potential in regenerative medicine in multiple organs. We suggest that the CSF1-Fc conjugate retains this potential, and may permit daily delivery by injection rather than continuous infusion required for the core molecule

The development and maintenance of the mononuclear phagocyte system of the chick is controlled by signals from the macrophage colony-stimulating factor (CSF1) receptor

BACKGROUND: Macrophages have many functions in development and homeostasis as well as innate immunity. Recent studies in mammals suggest that cells arising in the yolk sac give rise to self-renewing macrophage populations that persist in adult tissues. Macrophage proliferation and differentiation is controlled by macrophage colony-stimulating factor (CSF1) and interleukin 34 (IL34), both agonists of the CSF1 receptor (CSF1R). In the current manuscript we describe the origin, function and regulation of macrophages, and the role of CSF1R signaling during embryonic development, using the chick as a model. RESULTS: Based upon RNA-sequencing comparison to bone marrow-derived macrophages grown in CSF1, we show that embryonic macrophages contribute around 2% of the total embryo RNA in day 7 chick embryos, and have similar gene expression profiles to bone marrow-derived macrophages. To explore the origins of embryonic and adult macrophages, we injected Hamburger-Hamilton stage 16 to 17 chick embryos with either yolk sac-derived blood cells, or bone marrow cells from EGFP(+) donors. In both cases, the transferred cells gave rise to large numbers of EGFP(+) tissue macrophages in the embryo. In the case of the yolk sac, these cells were not retained in hatched birds. Conversely, bone marrow EGFP(+) cells gave rise to tissue macrophages in all organs of adult birds, and regenerated CSF1-responsive marrow macrophage progenitors. Surprisingly, they did not contribute to any other hematopoietic lineage. To explore the role of CSF1 further, we injected embryonic or hatchling CSF1R-reporter transgenic birds with a novel chicken CSF1-Fc conjugate. In both cases, the treatment produced a large increase in macrophage numbers in all tissues examined. There were no apparent adverse effects of chicken CSF1-Fc on embryonic or post-hatch development, but there was an unexpected increase in bone density in the treated hatchlings. CONCLUSIONS: The data indicate that the yolk sac is not the major source of macrophages in adult birds, and that there is a macrophage-restricted, self-renewing progenitor cell in bone marrow. CSF1R is demonstrated to be limiting for macrophage development during development in ovo and post-hatch. The chicken provides a novel and tractable model to study the development of the mononuclear phagocyte system and CSF1R signaling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-015-0121-9) contains supplementary material, which is available to authorized users

Energy Efficient Rate Adaptation Algorithm for FiWi Access Network

Abstract Similar to any telecommunication network, energy efficiency is a desirable feature for fiber wireless (FiWi) access networks. These networks have optical back end and wireless front end. Both ends may contribute for energy efficiency. This work focuses on front end of FiWi access network, which is IEEE 802.11a wireless local area network (WLAN). For energy saving WLAN uses power saving mode (PSM), in which sleeping opportunity of a station is increased. During sleep time, station remains switched off and results in reduction in energy required. However, it is also observed that during active period of transmission considerable energy is consumed, which is the function of rate of data transmission. More data rate results in more active energy consumption but less transmission delay and vice versa. In order to reduce active and hence total energy consumption, we tried to transmit the data at lower data rate, while maintaining transmission delay in tolerable limit. This paper presents an Energy Efficient Rate Adaptation Algorithm (EERAA) for the front end of fiber wireless access networks. Simulation results compare the energy efficiency and transmission delay of EERAA and various existing fixed data rate schemes. Proposed scheme offers good trade-off between energy efficiency and transmission delay

Energy Efficient Rate Adaptation Algorithm for FiWi Access Network

<div><p>Abstract Similar to any telecommunication network, energy efficiency is a desirable feature for fiber wireless (FiWi) access networks. These networks have optical back end and wireless front end. Both ends may contribute for energy efficiency. This work focuses on front end of FiWi access network, which is IEEE 802.11a wireless local area network (WLAN). For energy saving WLAN uses power saving mode (PSM), in which sleeping opportunity of a station is increased. During sleep time, station remains switched off and results in reduction in energy required. However, it is also observed that during active period of transmission considerable energy is consumed, which is the function of rate of data transmission. More data rate results in more active energy consumption but less transmission delay and vice versa. In order to reduce active and hence total energy consumption, we tried to transmit the data at lower data rate, while maintaining transmission delay in tolerable limit. This paper presents an Energy Efficient Rate Adaptation Algorithm (EERAA) for the front end of fiber wireless access networks. Simulation results compare the energy efficiency and transmission delay of EERAA and various existing fixed data rate schemes. Proposed scheme offers good trade-off between energy efficiency and transmission delay.</p></div