Eotaxin contributes to renal interstitial eosinophilia.

Background. A potent eosinophil chemotactic cytokine, human eotaxin, is directly chemotactic for eosinophils. Therefore, the specific expression of eotaxin in tissue might play a crucial role in tissue eosinophilia. However, the precise molecular mechanism of the Introduction recruitment and activation of eosinophils in human renal diseases remains to be investigated. We evaluated Eosinophils play an important role in various types of the role of eotaxin in the pathogenesis of human diVuse human disease including allergic, inflammatory, maliginterstitial nephritis with marked infiltration of nant and cardiovascular disorders [1]. In contrast, eosinophils. aberrantly activated eosinophils release toxic cationic Methods. In this study, we examined 20 healthy volun- proteins to induce tissue destruction [1]. Eosinoteers, 56 patients with primary or secondary glomerular phils produce cytokines [interleukin (IL)-3, IL-5 and diseases and two hypereosinophilic syndrome patients granulocyte-macrophage colony stimulating factor without renal involvement. Urinary and serum eotaxin (GM-CSF )] and lipid mediators (platelet-activating levels were determined by an enzyme-linked immuno- factor, leukotrien B4), which contribute to the sorbent assay. We also detected the presence of eotaxin inflammatory processes [1]. Therefore, an imbalance protein immunohistochemically. towards excess activation may lead to tissue destrucResults. On the one hand, urinary levels of eotaxin tion. In addition, since eosinophils are circulating were significantly higher before the initiation of gluco- leukocytes, some mediators would be necessary to corticoid administration in the patient with interstitial regulate eosinophil—endothelial cell interaction, nephritis with marked infiltration of eosinophils. On resulting in the infiltration and activation of eosinophils the other hand, urinary eotaxin levels were not detected in the tissue. However, the precise molecular mechanin any patients with nephrotic syndrome, interstitial ism of the recruitment and activation of tissue eosinonephritis without eosinophils, hypereosinophilic syn- phils remains to be investigated. drome without renal involvement or other renal dis- A chemokine, human eotaxin, has been reported to eases. Serum eotaxin levels were not detected in any be an early response gene of cytokine-stimulated epiof the patients. Therefore, the detection of eotaxin in thelial and endothelial cells, and is expressed in leukothe urine was specific for renal interstitial eosinophilia. cytes including eosinophils [2,3]. Eotaxin is directly Moreover, endothelial cells, infiltrating mononuclear chemotactic for eosinophils, but not mononuclear cells cells and renal epithelial cells in the tubulointerstitial or neutrophils. Thus, the specific expression of eotaxin lesions were immunostained with specific anti-eotaxin in the tissue might play a crucial role in tissue eosinoantibodies. Furthermore, the elevated urinary levels of philia accompanied by the activation of adhesion moleeotaxin decreased dramatically during glucocorticoid- cules. Recent studies indicate that eotaxin is expressed induced convalescence. in some organs including kidneys [2]. However, the Hypothesis. We hypothesize that in situ expression of role of eotaxin in the pathogenesis of human renal eotaxin may provide a new mechanism to explain the diseases has not yet been investigated. renal interstitial eosinophil infiltration. In order to examine whether locally produced eotaxin participates in the pathophysiology of human renal diseases by recruiting and activating eosinophils,