Fas death receptor signaling represses monocyte numbers and macrophage activation in vivo

Nathaniel J. Brown, Jack Hutcheson, Emily Bickel, John C. Scatizzi, Lee D. Albee, G. Kenneth Haines, Joy Eslick, Kathleen Bradley, Elsa Taricone, Harris Perlman

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Over 1 billion monocytes are produced daily, with a small percentage differentiating into macrophages, suggesting that excess monocytes are deleted through a tightly regulated process. Although the in vivo mechanism governing monocyte/macrophage homeostasis is unknown, deletion of monocytes in culture is mediated by the Fas death pathway and is blocked by M-CSF. To determine the in vivo significance of Fas in monocyte development, mice lacking Fas (lpr/lpr) and mice deficient in Fas and M-CSF were examined. Compared with congenic control C57BL/6 (B6) mice, lpr/lpr mice displayed increased numbers of circulating monocyies. The lack of Fas in M-CSF-deficient mice resulted in an enhanced percentage, but not total numbers, of monocytes. Fas deficiency led to an increase in myeloid bone marrow progenitor potential only in M-CSF-intact mice. Although lpr/lpr and B6 mice had similar numbers of tissue macrophages, the loss of Fas in M-CSF-deficient mice was sufficient to increase the number of macrophages in a subset of tissues. Additionally, after stimulation with thioglycolate, lpr/lpr and B6 mice showed equivalent numbers of peritoneal macrophages. However, Fas-deficient peritoneal macrophages displayed a marked increase in spontaneous and LPS-induced proinflammatory molecule production. Moreover, Fas-deficient mice showed enhanced systemic inflammatory arthritis associated with up-regulation of IL-1β and CCL2 secretion,'elevated numbers of inflammatory monocytes, and increased numbers of tissue macrophages. Collectively, these data suggest that Fas may be required for maintaining circulating monocytes and for suppressing macrophage activation and recruitment that are stimulus dependent.

Original languageEnglish (US)
Pages (from-to)7584-7593
Number of pages10
JournalJournal of Immunology
Volume173
Issue number12
StatePublished - Dec 15 2004

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CD95 Antigens
Death Domain Receptors
Macrophage Activation
Monocytes
Macrophage Colony-Stimulating Factor
Macrophages
Peritoneal Macrophages
Thioglycolates
Interleukin-1
Arthritis
Homeostasis
Up-Regulation
Bone Marrow

ASJC Scopus subject areas

  • Immunology

Cite this

Brown, N. J., Hutcheson, J., Bickel, E., Scatizzi, J. C., Albee, L. D., Haines, G. K., ... Perlman, H. (2004). Fas death receptor signaling represses monocyte numbers and macrophage activation in vivo. Journal of Immunology, 173(12), 7584-7593.

Fas death receptor signaling represses monocyte numbers and macrophage activation in vivo. / Brown, Nathaniel J.; Hutcheson, Jack; Bickel, Emily; Scatizzi, John C.; Albee, Lee D.; Haines, G. Kenneth; Eslick, Joy; Bradley, Kathleen; Taricone, Elsa; Perlman, Harris.

In: Journal of Immunology, Vol. 173, No. 12, 15.12.2004, p. 7584-7593.

Research output: Contribution to journalArticle

Brown, NJ, Hutcheson, J, Bickel, E, Scatizzi, JC, Albee, LD, Haines, GK, Eslick, J, Bradley, K, Taricone, E & Perlman, H 2004, 'Fas death receptor signaling represses monocyte numbers and macrophage activation in vivo', Journal of Immunology, vol. 173, no. 12, pp. 7584-7593.
Brown NJ, Hutcheson J, Bickel E, Scatizzi JC, Albee LD, Haines GK et al. Fas death receptor signaling represses monocyte numbers and macrophage activation in vivo. Journal of Immunology. 2004 Dec 15;173(12):7584-7593.
Brown, Nathaniel J. ; Hutcheson, Jack ; Bickel, Emily ; Scatizzi, John C. ; Albee, Lee D. ; Haines, G. Kenneth ; Eslick, Joy ; Bradley, Kathleen ; Taricone, Elsa ; Perlman, Harris. / Fas death receptor signaling represses monocyte numbers and macrophage activation in vivo. In: Journal of Immunology. 2004 ; Vol. 173, No. 12. pp. 7584-7593.
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