Methylcobalamin receptor The growth of macrophages from

The growth of macrophages from bone marrow Methylcobalamin receptor using recombinant CSF-1 has been described previously for human, mouse, chicken and pig bone marrow cells [7], [17], [50], [52], [53], [54]. Culture of feline macrophages is a valuable tool to allow the in vitro study of the effects of drugs, e.g. chemotherapeutic agents, which may cause immune-suppression or immune-modulation in cats. Equally, the mechanisms of feline infectious diseases that can infect macrophages, e.g. FIV or mycobacteria, may be further investigated. It will be of interest to compare the response of feline BMDMs to LPS in a similar fashion to the analysis performed for mice, human and porcine BMDMs [50], [55]. We have demonstrated previously that both recombinant human and porcine CSF-1 proteins can activate feline and canine CSF-1Rs using bone marrow aspirates [2]. The primary marrow cells used in the present study were harvested post-mortem, by repeated flushing from the femur. An earlier study Daniel et al. [56] noted that feline primary bone marrow cultures could be successfully maintained without the addition of exogenous CSF-1 due to the production of CSF-1 by the adherent bone-marrow cell population. This is a rather less-reproducible and inefficient approach. Bone-marrow cells can be frozen and thawed, so that cells preserved from a small number of animals can provide a long term resource for studies of macrophage biology. Recent studies investigating the effects of mesenchymal stem cell (MSC) therapy in rodent models including chronic renal failure and glomerulonephritis have demonstrated that MSC therapy can result in beneficial effects [57], [58]. In cats, autologous intra-renal injections of either adipose tissue-derived or bone-marrow-derived mesenchymal stem cells demonstrated modest improvements in glomerular filtration rate (GFR) and serum biochemical markers of renal disease [59]. MSCs are highly proliferative, undifferentiated cells that can self-renew [60], [61]. Due to these properties, MSCs are being suggested as therapeutic options for a range of diseases including chronic renal failure in cats [59], [62]. CSF-1 mRNA and protein are constitutively expressed [63], [64], [65] and, given the trophic functions, would be candidate mediators of some of the effects of MSC. Previous studies using non-species-specific colony stimulating factors for therapy have been hampered by the development of auto-antibodies. For example, the administration of rhGM-CSF to healthy dogs has been reported to produce neutralising antibodies after 10–12days [66]. Similarly, the administration of rhGM-CSF to cats with FIV triggered neutralising antibodies in 75% of the cats, 35days after a 2-week treatment protocol [67]. A practical therapy for cats based upon CSF-1R agonist is likely to involve the production of the species-specific protein, but this is costly. For therapeutic trials, our data shows that human and pig CSF-1 or IL-34 would have similar efficacy and could be considered for potential therapy. For acute therapy, the generation of neutralising antibodies may not be a significant issue.