Modulation of CSF-1-regulated post-natal development with anti-CSF-1 antibody

Suwen Wei, Daniel Lightwood, Heather Ladyman, Sue Cross, Helen Neale, Meryn Griffiths, Ralph Adams, Diane Marshall, Alastair Lawson, Andrew J. McKnight, E. Richard Stanley

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Colony-stimulating factor-1 (CSF-1) regulates the survival, proliferation and differentiation of macrophages. CSF-1-deficient mice are osteopetrotic due to a lack of osteoclasts, while their tissue macrophage deficiencies and an absence of CSF-1 regulation of CSF-1 receptor-expressing cells in the female reproductive tract contribute to their pleiotropic phenotype. To further understand CSF-1 regulation of macrophages in vivo, we developed a neutralizing anti-mouse CSF-1 antibody which was expressed as a recombinant Fab′ fragment and coupled to 40 kDa polyethylene glycol. As developmental regulation by CSF-1 is highest during the early post-natal period, the ability of this anti-CSF-1 reagent to inhibit development was tested by regular subcutaneous injection of mice from post-natal days 0.5-57.5. Antibody treatment decreased growth rate, decreased osteoclast number, induced osteopetrosis, decreased macrophage density in bone marrow, liver, dermis, synovium and kidney and decreased adipocyte size in adipose tissue, thereby inducing phenotypes shared by CSF-1- and CSF-1 receptor-deficient mice. While the antibody blocked macrophage development in some tissues, macrophage densities in other tissues were initially high and were reduced by treatment, proving that the antibody also blocked macrophage maintenance. Since cell surface CSF-1 is sufficient for the maintenance of normal synovial macrophage densities, these studies suggest that anti-CSF-1 Fab′-PEG efficiently neutralizes all three CSF-1 isoforms in vivo, namely the secreted proteoglycan, secreted glycoprotein and cell surface glycoprotein. Since CSF-1 has been shown to enhance chronic disease development in a number of mouse model systems, these studies demonstrate the feasibility of neutralizing CSF-1 effects in these models with an anti-CSF-1 antibody.

Original languageEnglish (US)
Pages (from-to)109-119
Number of pages11
JournalImmunobiology
Volume210
Issue number2-4
DOIs
StatePublished - Aug 19 2005

Fingerprint

Macrophage Colony-Stimulating Factor
Antibodies
Macrophages
Osteoclasts
Colony-Stimulating Factor Receptors
Maintenance
Osteopetrosis
Phenotype
Immunoglobulin Fab Fragments
Synovial Membrane
Membrane Glycoproteins
Feasibility Studies
Proteoglycans
Subcutaneous Injections
Dermis
Adipocytes

Keywords

  • Adipocyte
  • Anti-CSF-1 antibody
  • CSF-1
  • Macrophage
  • Osteoclast
  • Osteopetrosis
  • Post-natal development

ASJC Scopus subject areas

  • Immunology

Cite this

Wei, S., Lightwood, D., Ladyman, H., Cross, S., Neale, H., Griffiths, M., ... Stanley, E. R. (2005). Modulation of CSF-1-regulated post-natal development with anti-CSF-1 antibody. Immunobiology, 210(2-4), 109-119. https://doi.org/10.1016/j.imbio.2005.05.005

Modulation of CSF-1-regulated post-natal development with anti-CSF-1 antibody. / Wei, Suwen; Lightwood, Daniel; Ladyman, Heather; Cross, Sue; Neale, Helen; Griffiths, Meryn; Adams, Ralph; Marshall, Diane; Lawson, Alastair; McKnight, Andrew J.; Stanley, E. Richard.

In: Immunobiology, Vol. 210, No. 2-4, 19.08.2005, p. 109-119.

Research output: Contribution to journalArticle

Wei, S, Lightwood, D, Ladyman, H, Cross, S, Neale, H, Griffiths, M, Adams, R, Marshall, D, Lawson, A, McKnight, AJ & Stanley, ER 2005, 'Modulation of CSF-1-regulated post-natal development with anti-CSF-1 antibody', Immunobiology, vol. 210, no. 2-4, pp. 109-119. https://doi.org/10.1016/j.imbio.2005.05.005
Wei S, Lightwood D, Ladyman H, Cross S, Neale H, Griffiths M et al. Modulation of CSF-1-regulated post-natal development with anti-CSF-1 antibody. Immunobiology. 2005 Aug 19;210(2-4):109-119. https://doi.org/10.1016/j.imbio.2005.05.005
Wei, Suwen ; Lightwood, Daniel ; Ladyman, Heather ; Cross, Sue ; Neale, Helen ; Griffiths, Meryn ; Adams, Ralph ; Marshall, Diane ; Lawson, Alastair ; McKnight, Andrew J. ; Stanley, E. Richard. / Modulation of CSF-1-regulated post-natal development with anti-CSF-1 antibody. In: Immunobiology. 2005 ; Vol. 210, No. 2-4. pp. 109-119.
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