Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation

Mei Huei Jang, Deborah M. Herber, Xinnong Jiang, Sayan Nandi, Xu Ming Dai, Geraldine Zeller, E. Richard Stanley, Vicki R. Kelley

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

CSF-1, the major regulator of macrophage (Mφ) development, has three biologically active isoforms: a membrane-spanning, cell surface glycoprotein, a secreted glycoprotein, and a secreted proteoglycan. We hypothesized that there are shared and unique roles of individual CSF-1 isoforms during renal inflammation. To test this, we evaluated transgenic mice only expressing the cell surface or precursors of the secreted CSF-1 isoforms for Mφ accumulation, activation, and Mφ-mediated tubular epithelial cell (TEC) apoptosis during unilateral ureteral obstruction. The only difference between secreted proteoglycan and secreted glycoprotein CSF-1 isoforms is the presence (proteoglycan) or absence (glycoprotein) of an 18-kDa chondroitin sulfate glycosaminoglycan. We report that 1) cell surface CSF-1 isoform is sufficient to restore Mφ accumulation, activation, and TEC apoptosis to wild-type levels and is substantially more effective than the secreted CSF-1 isoforms; 2) the chondroitin sulfate glycosaminoglycan facilitates Mφ accumulation, activation, and TEC apoptosis; 3) increasing the level of secreted proteoglycan CSF-1 in serum amplifies renal inflammation; and 4) cell-cell contact is required for Mφ to up-regulate CSF-1-dependent expression of IFN-γ. Taken together, we have identified central roles for the cell surface CSF-1 and the chondroitin sulfate chain on secreted proteoglycan CSF-1 during renal inflammation.

Original languageEnglish (US)
Pages (from-to)4055-4063
Number of pages9
JournalJournal of Immunology
Volume177
Issue number6
StatePublished - Sep 15 2006

Fingerprint

Macrophage Colony-Stimulating Factor
Protein Isoforms
Inflammation
Kidney
Proteoglycans
Glycoproteins
Epithelial Cells
Apoptosis
Ureteral Obstruction
Chondroitin Sulfates
Membrane Glycoproteins
Transgenic Mice
Up-Regulation
Macrophages

ASJC Scopus subject areas

  • Immunology

Cite this

Jang, M. H., Herber, D. M., Jiang, X., Nandi, S., Dai, X. M., Zeller, G., ... Kelley, V. R. (2006). Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation. Journal of Immunology, 177(6), 4055-4063.

Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation. / Jang, Mei Huei; Herber, Deborah M.; Jiang, Xinnong; Nandi, Sayan; Dai, Xu Ming; Zeller, Geraldine; Stanley, E. Richard; Kelley, Vicki R.

In: Journal of Immunology, Vol. 177, No. 6, 15.09.2006, p. 4055-4063.

Research output: Contribution to journalArticle

Jang, MH, Herber, DM, Jiang, X, Nandi, S, Dai, XM, Zeller, G, Stanley, ER & Kelley, VR 2006, 'Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation', Journal of Immunology, vol. 177, no. 6, pp. 4055-4063.
Jang MH, Herber DM, Jiang X, Nandi S, Dai XM, Zeller G et al. Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation. Journal of Immunology. 2006 Sep 15;177(6):4055-4063.
Jang, Mei Huei ; Herber, Deborah M. ; Jiang, Xinnong ; Nandi, Sayan ; Dai, Xu Ming ; Zeller, Geraldine ; Stanley, E. Richard ; Kelley, Vicki R. / Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation. In: Journal of Immunology. 2006 ; Vol. 177, No. 6. pp. 4055-4063.
@article{0ee7044b0d2046ecaf8811b74363b56e,
title = "Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation",
abstract = "CSF-1, the major regulator of macrophage (Mφ) development, has three biologically active isoforms: a membrane-spanning, cell surface glycoprotein, a secreted glycoprotein, and a secreted proteoglycan. We hypothesized that there are shared and unique roles of individual CSF-1 isoforms during renal inflammation. To test this, we evaluated transgenic mice only expressing the cell surface or precursors of the secreted CSF-1 isoforms for Mφ accumulation, activation, and Mφ-mediated tubular epithelial cell (TEC) apoptosis during unilateral ureteral obstruction. The only difference between secreted proteoglycan and secreted glycoprotein CSF-1 isoforms is the presence (proteoglycan) or absence (glycoprotein) of an 18-kDa chondroitin sulfate glycosaminoglycan. We report that 1) cell surface CSF-1 isoform is sufficient to restore Mφ accumulation, activation, and TEC apoptosis to wild-type levels and is substantially more effective than the secreted CSF-1 isoforms; 2) the chondroitin sulfate glycosaminoglycan facilitates Mφ accumulation, activation, and TEC apoptosis; 3) increasing the level of secreted proteoglycan CSF-1 in serum amplifies renal inflammation; and 4) cell-cell contact is required for Mφ to up-regulate CSF-1-dependent expression of IFN-γ. Taken together, we have identified central roles for the cell surface CSF-1 and the chondroitin sulfate chain on secreted proteoglycan CSF-1 during renal inflammation.",
author = "Jang, {Mei Huei} and Herber, {Deborah M.} and Xinnong Jiang and Sayan Nandi and Dai, {Xu Ming} and Geraldine Zeller and Stanley, {E. Richard} and Kelley, {Vicki R.}",
year = "2006",
month = "9",
day = "15",
language = "English (US)",
volume = "177",
pages = "4055--4063",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation

AU - Jang, Mei Huei

AU - Herber, Deborah M.

AU - Jiang, Xinnong

AU - Nandi, Sayan

AU - Dai, Xu Ming

AU - Zeller, Geraldine

AU - Stanley, E. Richard

AU - Kelley, Vicki R.

PY - 2006/9/15

Y1 - 2006/9/15

N2 - CSF-1, the major regulator of macrophage (Mφ) development, has three biologically active isoforms: a membrane-spanning, cell surface glycoprotein, a secreted glycoprotein, and a secreted proteoglycan. We hypothesized that there are shared and unique roles of individual CSF-1 isoforms during renal inflammation. To test this, we evaluated transgenic mice only expressing the cell surface or precursors of the secreted CSF-1 isoforms for Mφ accumulation, activation, and Mφ-mediated tubular epithelial cell (TEC) apoptosis during unilateral ureteral obstruction. The only difference between secreted proteoglycan and secreted glycoprotein CSF-1 isoforms is the presence (proteoglycan) or absence (glycoprotein) of an 18-kDa chondroitin sulfate glycosaminoglycan. We report that 1) cell surface CSF-1 isoform is sufficient to restore Mφ accumulation, activation, and TEC apoptosis to wild-type levels and is substantially more effective than the secreted CSF-1 isoforms; 2) the chondroitin sulfate glycosaminoglycan facilitates Mφ accumulation, activation, and TEC apoptosis; 3) increasing the level of secreted proteoglycan CSF-1 in serum amplifies renal inflammation; and 4) cell-cell contact is required for Mφ to up-regulate CSF-1-dependent expression of IFN-γ. Taken together, we have identified central roles for the cell surface CSF-1 and the chondroitin sulfate chain on secreted proteoglycan CSF-1 during renal inflammation.

AB - CSF-1, the major regulator of macrophage (Mφ) development, has three biologically active isoforms: a membrane-spanning, cell surface glycoprotein, a secreted glycoprotein, and a secreted proteoglycan. We hypothesized that there are shared and unique roles of individual CSF-1 isoforms during renal inflammation. To test this, we evaluated transgenic mice only expressing the cell surface or precursors of the secreted CSF-1 isoforms for Mφ accumulation, activation, and Mφ-mediated tubular epithelial cell (TEC) apoptosis during unilateral ureteral obstruction. The only difference between secreted proteoglycan and secreted glycoprotein CSF-1 isoforms is the presence (proteoglycan) or absence (glycoprotein) of an 18-kDa chondroitin sulfate glycosaminoglycan. We report that 1) cell surface CSF-1 isoform is sufficient to restore Mφ accumulation, activation, and TEC apoptosis to wild-type levels and is substantially more effective than the secreted CSF-1 isoforms; 2) the chondroitin sulfate glycosaminoglycan facilitates Mφ accumulation, activation, and TEC apoptosis; 3) increasing the level of secreted proteoglycan CSF-1 in serum amplifies renal inflammation; and 4) cell-cell contact is required for Mφ to up-regulate CSF-1-dependent expression of IFN-γ. Taken together, we have identified central roles for the cell surface CSF-1 and the chondroitin sulfate chain on secreted proteoglycan CSF-1 during renal inflammation.

UR - http://www.scopus.com/inward/record.url?scp=33748493394&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748493394&partnerID=8YFLogxK

M3 - Article

VL - 177

SP - 4055

EP - 4063

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -