Modulation of CD93 molecule in a human monocyte-like cell line (U937) treated with nickel

ニッケルで処理されたヒト単球系細胞株(U937)におけるCD93 分子の動態を解析した。ニッケル処理はU937 細胞に対してインターロイキン-8(IL-8) の産生を増強しながらアポトーシスを誘導した。また、ニッケル処理によりU937 細胞表面上のCD93 分子(mCD93)の発現は有意に減少し、可溶性CD93 分子(sCD93)の産生は有意に増強した。以上の結果は、CD93 分子の動態が金属(ニッケル)アレルギーの発症メカニズムを解析するための新たなバイオマーカーに成り得ることを示唆している。In this study, we demonstrated the modulation of CD93 molecules (both membrane-bound and soluble-form) in a human monocyte-like cell line, U937 treated with nickel (Ni2+) to model contact hypersensitivity (CHS), such as metal allergy. Ni2+ induced the apoptosis of the U937 cells accompanied by the enhanced secretion of an inflammatory cytokine, interleukin-8 (IL-8). The percentages and mean fluorescence intensities (MFIs) of membrane-bound CD93 (mCD93) expressed on U937 cells were significantly decreased after treatment with Ni2+ when examined using flow cytometry with a CD93 monoclonal antibody (mAb) (mNI-11), which was established in our laboratories. In contrast, the secretion of soluble-form CD93 (sCD93) from U937 cells increased markedly after treatment with Ni2+. Taken together, these findings suggest that the modulation of CD93 molecules (both mCD93 and sCD93) might serve as a new biomarker for analyzing the inflammatory reaction in CHS induced by Ni2+

Serum levels of soluble CD93 in patients with chronic renal failure

慢性腎不全（CRF）患者における可溶性CD93（sCD93）の血清レベルを自主開発した抗ヒトCD93抗体（mNI-11）とオリジナル構築酵素抗体法（EIAキット）を用いて検討した。その結果、CRF患者血清中のsCD93は健康人と比較して有意に高値を示した。また、血清中インターロイキン-6（IL-6）もCRF患者は健康人に比較して有意に高値を示した。CRF患者血清中のsCD93と腎機能マーカーである尿素窒素、血清クレアチニン、血清シスタチンCとの相関を解析したところ、いずれも強い相関を示した。特に血清シスタチンCとはより強い相関を示した（r＝0.903、P＜0.001）。以上の結果から、CRF患者血清中のsCD93は、特に血清シスタチンCとの相関性がより強いことから、早期の腎障害を検出する新規のバイオマーカーになることがわかった。In this clinical study, we examined the serum levels of soluble CD93 (sCD93) in patients with chronic renal failure (CRF) by an originally constructed enzyme-linked immunoassay (EIA) using a CD93 monoclonal antibody (mAb) (mNI-11) established in our laboratories. The serum concentrations of sCD93 in patients with CRF were significantly higher (P < 0.001) than those in normal healthy controls. Furthermore, the serum levels of interleukin-6 (IL-6) were also significantly higher in the patients with CRF (P < 0.05) than in the normal healthy controls. In addition, the serum levels of sCD93 were strongly correlated with the blood urea nitrogen (BUN) (r = 0.797, P < 0.001), serum creatinine (r = 0.784, P < 0.001) and serum cystatin C (r = 0.913, P < 0.001). Taken together, these findings suggest that the serum sCD93 may serve as a new biomarker for analyzing or measuring renal function