Shedding as a mechanism of down-modulation of CD14 on stimulated human monocytes.
Shedding as a mechanism of down-modulation of CD14 on stimulated human monocytes.
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DOI：
10.4049/jimmunol.147.5.1567
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发表时间：
1991-09
影响因子：
4.4
通讯作者：
V. Bažil;J. Strominger
中科院分区：
文献类型：
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作者：
V. Bažil;J. Strominger
CD14作为磷脂连接蛋白在单核细胞表面表达，是血清LPS结合蛋白/LPS复合物的受体。在受到生理激活/分化剂如细菌LPS和ifn - γ、药理剂PMA和钙离子载体A23187以及抗cd14抗体的刺激后，单核细胞特异性下调。蛋白酶抑制剂氟磷酸二异丙基和PMSF在4℃或pH 4.5时几乎完全阻断了下调，并显著抑制了下调。从表面碘化单核细胞活化后的培养上清中分离出可溶性标记CD14，表明CD14从细胞表面脱落而不是内化。体外单核细胞脱落的可溶性CD14的大小比膜结合形式或由磷脂酰肌醇特异性磷脂酶C从细胞表面切割的可溶性CD14的大小小，但与通常在人血清中发现的两种主要可溶性CD14形式之一的大小相同。这些数据表明，单核细胞刺激诱导的CD14脱落可能在调节表面CD14表达中起重要作用。
CD14, expressed on the surface of monocytes as a phospholipid-linked protein, is a receptor for serum LPS binding protein/LPS complex. It was specifically down-modulated after stimulation of monocytes by physiologic activating/differentiating agents such as bacterial LPS and IFN-gamma, by the pharmacologic agents PMA and calcium ionophore A23187, and by anti-CD14 antibodies. The down-modulation was almost totally blocked at 4 degrees C or at pH 4.5 and markedly inhibited by the protease inhibitors diisopropylfluorophosphate and PMSF. A soluble labeled CD14 was isolated from culture supernatant of surface iodinated monocytes after their activation, indicating that CD14 is shed from the cell surface rather than internalized. The size of the soluble CD14 shed from the monocytes in vitro was smaller than that of either the membrane-bound form or a soluble CD14 cleaved from the cell surface by phosphatidyl inositol-specific phospholipase C, but identical to the size of one of the two major soluble CD14 forms normally found in human serum. These data suggest that CD14 shedding induced by monocyte stimulation may play an important role in the regulation of surface CD14 expression.