Renal epithelial cell-derived monocyte colony stimulating factor as a local informant of renal injury and means of monocyte activation

Kimberly A. Singh, Robert L. Kampen, Steven C. Hoffmann, Shady M. Eldaif, Allan D. Kirk

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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.

Original languageEnglish
Pages (from-to)730-737
Number of pages8
JournalTransplant International
Issue number7
StatePublished - Jul 2009
Externally publishedYes


  • Kidney transplantation
  • Monocyte
  • Monocyte colony stimulating factor


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