Macrophages are not the source of injurious interleukin-18 in ischemic acute kidney injury in mice.

Abstract

We previously reported in ischemic acute kidney injury (AKI) in mice that caspase-1-mediated production of interleukin-18 (IL-18) is pathogenic and that macrophage depletion by liposome-encapsulated clodronate (LEC) is protective. Therefore, our aim was to determine whether macrophages are a source of IL-18 in ischemic AKI in mice. On immunofluorescence staining of the outer stripe of outer medulla, the number of macrophages double stained for CD11b and IL-18 was significantly increased in AKI and significantly decreased by LEC. Adoptive transfer of RAW 264.7 cells, a mouse macrophage line that constitutively expresses IL-18 mRNA, reversed the functional protection against AKI in both LEC-treated wild-type and caspase-1 -/- mice. To test whether IL-18 in macrophages is necessary to cause AKI, we adoptively transferred macrophages in which IL-18 was inhibited. Peritoneal macrophages isolated from wild-type mice, IL-18 binding protein transgenic (IL-18 BP Tg) mice, and IL-18 -/- mice were used. IL-18 BP Tg mice overexpress human IL-18 BP and exhibit decreased biological activity of IL-18. Adoptive transfer of peritoneal macrophages from wild-type as well as IL-18 BP Tg and IL-18 -/- mice reversed the functional protection against AKI in LEC-treated mice. In summary, adoptive transfer of RAW cells, that constitutively express IL-18, reverses the functional protection in macrophage-depleted wild-type and caspase-1 -/- mice with AKI. However, adoptive transfer of peritoneal macrophages in which IL-18 function was inhibited also reverses the functional protection in macrophage-depleted mice. In conclusion, IL-18 from adoptive transfer of macrophages is not sufficient to cause ischemic AKI.

• Authors: Zhibin He, Belda Dursun, Dong-Jin Oh, Lawrence Lu, Sarah Faubel, Charles L Edelstein
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 296 Issue 3 Pg. F535-42 (Mar 2009) ISSN: 1931-857X [Print] United States
• PMID: 19129255 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CD11b Antigen
• Interleukin-18
• RNA, Messenger
• Caspase 1

Topics

• Acute Kidney Injury (immunology, metabolism)
• Adoptive Transfer
• Animals
• CD11b Antigen (metabolism)
• Caspase 1 (metabolism)
• Cell Line
• Fluorescent Antibody Technique
• Interleukin-18 (metabolism)
• Kidney (metabolism)
• Killer Cells, Natural (metabolism)
• Macrophages, Peritoneal (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• RNA, Messenger (metabolism)