| First Author | Jang MH | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 6 | Pages | 4055-63 |
| PubMed ID | 16951369 | Mgi Jnum | J:138044 |
| Mgi Id | MGI:3804111 | Doi | 10.4049/jimmunol.177.6.4055 |
| Citation | Jang MH, et al. (2006) Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation. J Immunol 177(6):4055-63 |
| abstractText | CSF-1, the major regulator of macrophage (Mphi) 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 Mphi accumulation, activation, and Mphi-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 Mphi 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 Mphi 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 Mphi to up-regulate CSF-1-dependent expression of IFN-gamma. 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. |
