Reduction of natural killer and natural killer T cells is not protective in cisplatin-induced acute renal failure in mice

• Published in: Nephrology (Carlton, Vic.) Vic.), 2011-08, Vol.16 (6), p.545-551
• Main Authors: KIM, HYE-RYOUN, LEE, MI-KYUNG, PARK, AE-JA, PARK, EON-SEOB, KIM, DONG-SEOK, AHN, JIHYUN, KIM, JAETACK, KIM, SU-HYUN, OH, DONG-JIN
• Format: Article
• Language: English
• Subjects: acute kidney injury; Acute Kidney Injury - chemically induced; Acute Kidney Injury - immunology; Acute Kidney Injury - pathology; Acute Kidney Injury - prevention & control; Animals; Antibodies, Monoclonal - administration & dosage; Antigens, Ly - immunology; Apoptosis; Caspase 1 - metabolism; Chemokine CX3CL1 - metabolism; Chemotaxis, Leukocyte; Cisplatin; Disease Models, Animal; Flow Cytometry; Granzymes - metabolism; Immunohistochemistry; Kidney Tubular Necrosis, Acute - chemically induced; Kidney Tubular Necrosis, Acute - immunology; Kidney Tubular Necrosis, Acute - pathology; Kidney Tubular Necrosis, Acute - prevention & control; Kidney Tubules - immunology; Kidney Tubules - pathology; killer cells; Killer Cells, Natural - immunology; Mice; Mice, Inbred C57BL; natural; Natural Killer T-Cells - immunology; NK Cell Lectin-Like Receptor Subfamily B - immunology; NK Cell Lectin-Like Receptor Subfamily D - metabolism; Time Factors
• ISSN: 1320-5358; 1440-1797
• DOI: 10.1111/j.1440-1797.2011.01473.x

Aims:  A recent report showed that fractalkine (CX3CL1), which functions as both a potent chemoattractant and adhesion molecule for monocytes and natural killer (NK) cells was significantly increased in cisplatin‐induced acute renal failure (CisARF) in mice. Therefore, we developed the hypothesis that increased CX3CL1 expression in CisARF initiates NK cell infiltration in the kidney. The aim of the present study was to determine the role of NK cells in CisARF in mice. Methods:  Time course of pan‐NK positive cells in CisARF was investigated by using immunohistochemistry (IHC) for CD49b. Pan‐NK positive cells were reduced by using anti‐NK1.1 mAb. The model of pan‐NK positive cells reduction was confirmed by flow cytometry of the spleen and IHC of the kidney. The expression of granzyme A and caspase‐1 was examined, and the activity of caspase‐1 was also determined. We performed a study on whether there was significant protection of renal function after reduction of pan‐NK positive cells. Results:  (i) Infiltration of pan‐NK positive cells was prominent on day 3 after cisplatin administration. (ii) granzyme A expression was significantly increased in CisARF and CisARF+NK1.1 Ab compared to vehicle. (iii) Caspase‐1 expression and activity was significantly increased in CisARF mice compared to vehicle and CisARF+NK1.1 Ab. (iv) Reduction of pan‐NK positive cells was not protective in cisplatin‐induced acute renal failure in mice. Conclusions:  Although infiltration of pan‐NK cells was significantly increased in CisARF, reduction of infiltration of pan‐NK cells into the kidney was not protective against CisARF in mice. The investigators examined the nature of infiltrating leukocyte in a model of cisplantin‐induced ARF. Despite a significant infiltration of pan‐natural killer (NK) cells, reduction of infiltration of pan‐NK cells into the kidney was not protective against cisplatin‐induced acute renal failure in mice. The leukocyte recruitment could be secondary to the chemotactic effect of proteinuria.