title: Renal epithelial cell-derived monocyte colony stimulating factor as a local informant of renal injury and means of monocyte activation.
abstract: Monocyte accumulation in renal allografts is associated with allograft dysfunction. As monocyte influx occurs acutely following reperfusion, we investigated the effect of ischemia-reperfusion injury (IRI) on monocyte colony stimulating factor (m-CSF), a key cytokine in monocyte recruitment. We hypothesized that renal tubule epithelial cells (RTECs) could produce m-CSF in response to IRI, which could in turn promote monocyte activation. Real time PCR was used to measure levels of intragraft m-CSF transcripts in patients during IRI and clinical rejection. Also, m-CSF production by RTECs following IRI simulation in vitro was measured using ELISA. Monocyte expression of CD40 and CD80 was then analyzed using flow cytometry following co-culture with supernatants of RTECs after IRI. Monocyte expression of CD40, CD80 and HLA-DR was then examined following treatment with rh-m-CSF (10, 36, and 100 ng/ml), as was monocyte size and granularity. We found that intragraft m-CSF transcription was significantly increased postreperfusion (P = 0.002) and during clinical rejection (P = 0.002). We also found that RTECs produced m-CSF in response to IRI in vitro (P = 0.036). Monocytes co-cultured with the supernatants of postischemic RTECs became activated as evidenced by increased expression of CD40 and CD80. Also, monocytes treated with recombinant m-CSF assumed an activated phenotype exhibiting increased size, granularity and expression of CD40, CD80, CD86, and HLA-DR, and demonstrating enhanced phagocytic activity. Taken together, we suggest that renal tubular cell derived m-CSF is a stimulus for monocyte activation and may be an important target for control of IRI-associated immune activation.
authors.affiliation: Department of Surgery, Emory Transplant Center, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Singh
authors.forename: Robert L
authors.initials: RL
authors.lastname: Kampen
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hoffmann
authors.forename: Shady M
authors.initials: SM
authors.lastname: Eldaif
authors.forename: Allan D
authors.initials: AD
authors.lastname: Kirk
mesh_terms: D018122:B7-1 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology*; D005434:Flow Cytometry / Q000379:methods; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007511:Ischemia / Q000473:pathology; D007668:Kidney / Q000293:injuries* / Q000473:pathology*; D016030:Kidney Transplantation / Q000379:methods*; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D015424:Reperfusion
chemical_list: D018122:B7-1 Antigen; D019013:CD40 Antigens; D003115:Colony-Stimulating Factors; D006684:HLA-DR Antigens