Identification of lactoferrin as the granulocyte-derived inhibitor of colony-stimulating activity production
Identification of lactoferrin as the granulocyte-derived inhibitor of colony-stimulating activity production
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乳铁蛋白作为粒细胞来源的集落刺激活性产生抑制剂的鉴定
DOI：
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发表时间：
1978
影响因子：
15.3
通讯作者：
J. Exp
中科院分区：
文献类型：
--
作者：
H. Broxmeyer;Anthony Smithyman;Richard R Eger;Paul A. Meyers;Maria De Sousa;J. Exp
乳铁蛋白(Lactoferrin，LF)是一种存在于成熟粒细胞特定颗粒中的铁结合蛋白，是一种集落抑制因子(CIF)，在体外抑制单核细胞和巨噬细胞产生CsA，在体内抑制反弹粒细胞生成。通过等电聚焦分离LF和CIF，证实了抑制活性的区域都对应于pH值一致的6.5。此外，纯化的兔抗人LF抗血清的免疫球蛋白部分，而不是兔抗转铁蛋白(Tf)，使Lf和CIF抑制CsA产生的能力被预先与Lf中和浓度的Lf孵育所阻断。CsA产生的抑制与LF铁饱和有关；APO-Lf(去铁)仅在10(-7)M以上有效浓度，天然Lf(8%铁饱和)在10(-15)M时有效，而全铁饱和Lf在10(-17)M时被抑制。这一逆转依赖于LF对内毒素的相对浓度。血清Tf是一种生物化学上类似的铁结合蛋白，其抗原性不同于Lf，但仅在高于10(-6)M的浓度下具有最低的活性。Lf不抑制外源性刺激的人粒细胞和巨噬细胞集落形成细胞或依赖促红细胞生成素的人或小鼠红系集落形成细胞或红系爆裂细胞。微克剂量的LF体内作用于环磷酰胺预处理的CD1和C57BL/6小鼠，抑制CD1和C57BL/6小鼠的反弹粒系生成和CsA生成。这些结果强烈表明，Lf是粒细胞生成的一种生理调节因子。
Lactoferrin (LF), the iron-binding protein present in the specific granules of mature granulocytes has been identified as colony inhibitory factor (CIF) which suppresses granulocyte--macrophage colony stimulating activity (CSA) production by monocytes and macrophages in vitro and rebound granulopoiesis in vivo. Separation of LF and CIF by isoelectric focusing confirmed that the regions of inhibitory activity corresponded in both to a pH of congruent to 6.5. In addition, the purified immunoglobulin fraction of rabbit anti-human LF antiserum, but not rabbit anti-transferrin (TF), inactivated the capacity of LF and CIF to inhibit CSA production, an effect blocked by prior incubation of anti-LF with neutralizing concentrations of LF. Suppression of CSA production correlated with the iron-saturation of LF; APO-LF (depleted of iron) was only active concentrations greater than 10(-7) M, native LF (8% iron saturated) was active at 10(-15) M, and fully iron- saturated LF inhibited at 10(-17) M. Suppression of CSA production occurred within a 1/2-h preincubation period with human blood monocytes but was reversed by bacterial lipopolysaccharide (LPS). This reversal was dependent on the relative concentrations of LF to LPS. Serum TF, a biochemically similar iron-binding protein which is antigenically distinct from LF, was only minimally active at concentrations greater than 10(-6) M. LF did not inhibit exogenously stimulated human granylocyte and macrophage colony-forming cells or erythropoietin- dependent human or murine erythroid colony- or erythroid burst-forming cells. Microgram quantities of LF acted in vivo to inhibit rebound granulopoiesis and CSA production in CD1 and C57Bl/6 mice pretreated with cyclophosphamide. These results strongly implicate LF as a physiological regulator of granulopoiesis.