Regulation of MSCF receptors on microglia in the normal and injured mouse central nervous system: A quantitative immunofluorescence study using confocal laser microscopy

Raivich, Gennadij; Haas, Stefan; Werner, Alexander; Klein, Michael A.; Kloss, Christian U.A.; Kreutzberg, Georg W.

doi:10.1002/(sici)1096-9861(19980808)395:3<342::aid-cne6>3.0.co;2-2

Cited by 111 publications

(119 citation statements)

References 59 publications

(58 reference statements)

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…Quantitative studies distal to the lesion revealed an approximately proportional increase of both GFP ϩ and GFP Ϫ macrophages during the first days, correlating with the presence of numerous proliferating macrophages of either type that peaked 3 days after injury. These data reveal a remarkable similarity with lesion-induced microglial proliferation in the brain (Graeber et al, 1988;Raivich et al, 1998). After facial nerve injury, microglial proliferation in the facial nucleus exhibits a time course similar to macrophage proliferation in the sciatic nerve, and microglial numbers increase by about the same degree as resident macrophages do in our system.…”

Section: Resident Endoneurial Macrophages In Wallerian Degenerationsupporting

confidence: 69%

Macrophage Response to Peripheral Nerve Injury: The Quantitative Contribution of Resident and Hematogenous Macrophages

Mueller

Leonhard

Wacker

et al. 2003

Laboratory Investigation

221

185

View full text Add to dashboard Cite

SUMMARY:Whereas local microglial cells of the CNS rapidly respond to injury, little is known about the functional role of resident macrophages of the peripheral nervous system in nerve pathology. Using bone marrow chimeric rats, we recently identified individual resident endoneurial macrophages that rapidly became activated after nerve injury. However, the extent of local macrophage activation and its quantitative contribution to the total macrophage response is unknown. We now have created chimeric mice by transplanting bone marrow from green fluorescent protein (GFP)-transgenic mice into irradiated wild-type mice, allowing easy differentiation and quantification of hematogenous and resident endoneurial macrophages. After sciatic nerve crush injury, both GFP Ϫ and GFP ϩ resident macrophages, the latter having undergone physiological turnover from the blood before injury, rapidly underwent morphological alterations and increased in number. Proliferating GFP Ϫ and GFP ϩ resident macrophages were abundant and peaked 3 days after injury. A major lesion-induced influx of hematogenous macrophages with a disproportionate increase of GFP ϩ macrophages was not observed until Day 4. Throughout all time points examined, GFP Ϫ resident macrophages were strikingly frequent, reaching maximum numbers 9.5-fold above baseline. There was also a notable proportion of GFP Ϫ resident endoneurial macrophages phagocytosing myelin and expressing major histocompatibility complex class II. Our results demonstrate for the first time that the rapid response of resident endoneurial macrophages to nerve injury is quantitatively important and that local macrophages contribute significantly to the total endoneurial macrophage pool during Wallerian degeneration. (Lab Invest 2003, 83:175-185).

show abstract

Section: Resident Endoneurial Macrophages In Wallerian Degenerationsupporting

confidence: 69%

Macrophage Response to Peripheral Nerve Injury: The Quantitative Contribution of Resident and Hematogenous Macrophages

Mueller

Leonhard

Wacker

et al. 2003

Laboratory Investigation

221

185

View full text Add to dashboard Cite

show abstract

“…4 Odontoblasts and ameloblasts from wt/wt mice also expressed the expected 552 bp CSF-1 receptor fragment. 26 Normal murine spleen that contains macrophages provided a positive control for CSF-1 isoforms and receptor.…”

Section: Resultsmentioning

confidence: 99%

Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects

Werner

Gluhak-Heinrich

Woodruff

et al. 2007

Archives of Oral Biology

View full text Add to dashboard Cite

Objective-The aim of this study was to characterize the tooth phenotype of CSF-1-deficient op/ op mice and determine whether expression of csCSF-1 in these mice has a role in primary tooth matrix formation.Design-Ameloblasts and odontoblasts, isolated from wt/wt frozen sections using laser capture microdissection, were analyzed for csCSF-1, sCSF-1 and CSF-1R mRNA by RT-PCR. Mandibles, excised from 8 day op/op and wt/wt littermates, were examined for tooth morphology as well as amelogenin and DMP1 expression using in situ hybridization. Op/opCS transgenic mice, expressing csCSF-1 in teeth and bone using the osteocalcin promoter, were generated. Skeletal x-rays and histomorphometry were performed; teeth were analyzed for morphology and matrix proteins.Results-Normal dental cells in vivo express both CSF-1 isoforms and CSF-1R. Compared to wt/ wt, op/op teeth prior to eruption showed altered dental cell morphology and dramatic reduction in DMP1 transcripts. Op/opCS mice showed marked resolution of osteopetrosis, tooth eruption and teeth that resembled amelogenesis imperfecta-like phenotype. At 3 weeks, op/op teeth showed severe enamel and dentin defects and barely detectable amelogenin and DMP1. In op/opCS mice, DMP1 in odontoblasts increased to near normal and dentin morphology was restored; amelogenin also increased. Enamel integrity improved in op/opCS, although it was thinner than wt enamel.Conclusions-Results demonstrate that ameloblasts and odontoblasts are a source and potential target of CSF-1 isoforms in vivo. Expression of csCSF-1 within the tooth microenvironment is essential for normal tooth morphogenesis and may provide a mechanism for coordinating the process of tooth eruption with endogenous matrix formation.

show abstract

“…37,38,40 After peripheral axotomy, microglia in the facial motor nucleus increase their expression of M-CSF receptors and increase their binding of M-CSF and GM-CSF before or at the onset of microglial proliferation. 39,52 Although the presently observed up-regulation of M-CSF and M-CSF receptor mRNA levels 5 days after lesion occurs relatively late compared with the peak microglial proliferation 3 days after lesion, it should be taken into consideration that changes in mRNA levels were determined based on analysis of whole hippocampi, not allowing direct assessment of up-regulation of these molecules or the GM-CSF and GM-CSF receptor in the areas of microglial mitosis. M-CSF also plays an essential role in the maintenance of the microglial cell population in the normal adult CNS, 38 which is in line with studies of cultured microglia showing that deprivation of M-CSF results in microglial apoptosis.…”

mentioning

confidence: 99%

Population Control of Resident and Immigrant Microglia by Mitosis and Apoptosis

Wirenfeldt

Dissing-Olesen

Babcock

et al. 2007

The American Journal of Pathology

View full text Add to dashboard Cite

Microglial population expansion occurs in response to neural damage via processes that involve mitosis and immigration of bone marrow-derived cells. However, little is known of the mechanisms that regulate clearance of reactive microglia, when microgliosis diminishes days to weeks later. We have investigated the mechanisms of microglial population control in a welldefined model of reactive microgliosis in the mouse dentate gyrus after perforant pathway axonal lesion. Unbiased stereological methods and flow cytometry demonstrate significant lesion-induced increases in microglial numbers. Reactive microglia often occurred in clusters, some having recently incorporated bromodeoxyuridine, showing that proliferation had occurred. Annexin V labeling and staining for activated caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling showed that apoptotic mechanisms participate in dissolution of the microglial response. Using bone marrow chimeric mice, we found that the lesion-induced proliferative capacity of resident microglia superseded that of immigrant microglia, whereas lesion-induced kinetics of apoptosis were comparable. Microglial numbers and responses were severely reduced in bone marrow chimeric mice. These results broaden our understanding of the microglial response to neural damage by demonstrating that simultaneously occurring mitosis and apoptosis regulate expansion and reduction of both resident and immigrant microglial cell populations. (Am J Pathol

show abstract

Regulation of MSCF receptors on microglia in the normal and injured mouse central nervous system: A quantitative immunofluorescence study using confocal laser microscopy

Cited by 111 publications

References 59 publications

Macrophage Response to Peripheral Nerve Injury: The Quantitative Contribution of Resident and Hematogenous Macrophages

Macrophage Response to Peripheral Nerve Injury: The Quantitative Contribution of Resident and Hematogenous Macrophages

Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects

Population Control of Resident and Immigrant Microglia by Mitosis and Apoptosis

Contact Info

Product

Resources

About