Kinetics of antibody-dependent binding of haptenated phospholipid vesicles to a macrophage-related cell line.
Kinetics of antibody-dependent binding of haptenated phospholipid vesicles to a macrophage-related cell line.
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半抗原化磷脂囊泡与巨噬细胞相关细胞系的抗体依赖性结合动力学。
DOI：
10.1021/bi00564a036
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发表时间：
1980
期刊：
影响因子：
2.9
通讯作者：
McConnell,HM
中科院分区：
文献类型：
--
作者：
Lewis,JT;Hafeman,DG;McConnell,HM
J.托德刘易斯，* 迪恩G. Hafeman和Harden M. McConnell* 摘要：我们已经测量了半抗原化脂质囊泡与RAW 264巨噬细胞的特异性抗体依赖性结合（和吞噬作用）的动力学，其作为囊泡表面上的抗体密度和囊泡的脂质组成的函数。流体囊泡（37 ℃下的二肉豆蔻酰磷脂酰胆碱）比固体囊泡（37 ℃下的二棕榈酰磷脂酰胆碱）更快地与巨噬细胞结合.在二棕榈酰磷脂酰胆碱囊泡膜中包含胆固醇导致结合率的大幅度提高，而在二肉豆蔻酰磷脂酰胆碱膜中包含胆固醇具有小得多的作用（37 ℃）。囊泡结合的速率还取决于囊泡表面上的抗体密度。在细胞松弛素B的存在下，囊泡的吞噬作用在二肉豆蔻酰磷脂酰胆碱囊泡的情况下被完全抑制，在二棕榈酰磷脂酰胆碱囊泡的情况下被部分抑制。对囊泡与巨噬细胞结合动力学进行了分析，得出结论：受体在吞噬作用期间与囊泡一起沿着内化，并且这些受体在实验期间不被替换。数据的分析显示囊泡结合（和吞噬作用）和受体损失之间的指数关系，使得在较晚时间结合的囊泡比在较早时间结合的囊泡消耗更少的受体的巨噬细胞。二肉豆蔻酰磷脂酰胆碱和二棕榈酰磷脂酰胆碱囊泡与巨噬细胞结合速率的差异可以用与这些囊泡表面结合的抗体的侧向扩散系数的差异来解释。胆固醇在二棕榈酰磷脂酰胆碱膜上的加入增强了这种扩散系数。上述考虑被纳入一个简单的动力学模型的囊泡的结合速率的大分子。吞噬细胞与抗体包被的靶细胞的相互作用可以被认为是细胞-细胞识别和触发的一个例子。靶细胞上的抗原首先被特异性抗体“识别”;结合抗体的Fc茎被噬细胞的Fc受体“识别”，这反过来触发靶细胞的吞噬作用或细胞溶解。在目前的工作中，我们用半抗原化的脂质囊泡代替靶细胞，进一步简化了这种细胞-细胞识别的“模型”，因为这种囊泡的物理和化学性质可以相当精确地控制。通过改变这些物理和化学性质，并通过研究吞噬活性，人们可以希望更好地理解通常涉及细胞-细胞识别的分子事件。我们研究了囊泡靶膜中的分子运动与囊泡结合和/或被RAW 264巨噬细胞吞噬的动力学之间的关系。我们还试图提供动力学结果的定量分析。免疫系统细胞和半抗原化脂质膜之间特异性抗体依赖性相互作用的其他研究包括盖革和Schreiber（1979）、Henkart和布卢门塔尔（1975）以及Hafeman等人的工作。（1979年）。本研究已进行了平行的研究，特异性抗体依赖性激活的第一组分的补体类似的脂质靶膜的动力学。我们获得的半抗原化脂质靶膜的特异性抗体依赖性结合的结果与特异性抗-
J. Todd Lewis,* Dean G. Hafeman, and Harden M. McConnell* abstract: We have measured the kinetics of specific anti-body-dependent binding (and phagocytosis) of haptenated lipid vesicles to RAW264 macrophages as a function of antibody density on the vesicle surface and lipid composition of the vesicles. Fluid vesicles (dimyristoylphosphatidylcholine at 37 C) bindmuch more rapidly to macrophages than do solid vesicles (dipalmitoylphosphatidylcholine at 37 C). Inclusion of cholesterol in the dipalmitoylphosphatidylcholine vesicle membrane results in a large enhancement in binding rate, whereas inclusion of cholesterol in the dimyristoyl-phosphatidylcholine membrane has a much smaller effect (37 C). The rate of vesicle binding also depends on the antibody density on the vesicle surface. In the presence of cytochalasin B, vesicle phagocytosis is completelyinhibited in the case of dimyristoylphosphatidylcholine vesicles and partially inhibited in the case of dipalmitoylphosphatidylcholine vesicles. An analysis of the vesicle to macrophage binding kinetics has been made, leading to the conclusion that receptors are internalized along with vesicles during phagocytosis, and these receptors are not replaced during the time of the experiment. The analysis of the data shows an exponential relationship between vesicle binding (and phagocytosis) and receptor loss, such that vesicles binding at later times deplete the macrophage of fewer receptors than do vesicles binding at earlier times. The dif-ference in the rate of binding of dimyristoylphosphatidylcholine and dipalmitoylphosphatidylcholine vesicles to the macro-phages can be accounted for in terms of the difference in the lateral diffusion coefficients of antibodies bound to these vesicle surfaces. Theaddition of cholesterol to the dipalmitoyl-phosphatidylcholine membrane enhances this diffusion coef-ficient. The above considerations are incorporated into a simple kinetic model for the binding rates of vesicles to ma-crophages. e interaction of a phagocytic cell with an antibody-coated target cell can be thought of as an example of cell-cell rec-ognition and triggering. Antigens on the target cell are first “recognized” by specific antibodies; the Fc stems of the bound antibodies are “recognized” by the Fc receptors of the pha-gocytic cell, which in turn triggers phagocytosis or cytolysis of the target cell. In thepresent work we have simplified this “model” of cell-cell recognition even further by using hap-tenated lipid vesicles in place of the target cell, since the physical and chemical properties of such vesicles can be con-trolled with considerable precision. By varying these physical and chemical properties and by studying the phagocytic ac-tivity, one can hope to understand better the molecular events that are typically involved in cell-cell recognition. We have investigated the relation between molecular motion in the vesicle target membranes and the kinetics of vesicle binding and/or phagocytosis by RAW264 macrophages. We have also attempted to provide a quantitative analysis of the kinetic results. Other studies of specific antibody-dependent inter-actions between cells of the immune system and haptenated lipid membranes include work by Geiger & Schreiber (1979), Henkart & Blumenthal (1975), and Hafeman et al.(1979). The present study has been carried out in parallel with studies of the kinetics of specific antibody-dependent activation of the first component of complement by similar lipid target membranes. The results we have obtained for specific anti-body-dependent binding of haptenated lipid targetmembranes are strikingly similar to those observed for the specific anti-
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与模型膜中的脂质半抗原结合的抗体的扩散速度与脂质本身一样快。
DOI：
--
发表时间：
1979
影响因子：
11.1
作者：
L. M. Smith;J. W. Parce;B. Smith;H. Mcconnell
通讯作者：
H. Mcconnell
含有自旋标记脂质半抗原的脂质体对中性粒细胞的特异性抗体依赖性激活。
DOI：
--
发表时间：
1979
期刊：
Biochemical and Biophysical Research Communications - BBRC
影响因子：
--
作者：
D. Hafeman;J. W. Parce;H. Mcconnell
通讯作者：
H. Mcconnell
淋巴细胞与脂质双层膜的相互作用：淋巴细胞介导的靶细胞裂解模型。
DOI：
--
发表时间：
1975
影响因子：
11.1
作者：
P. Henkart;R. Blumenthal
通讯作者：
R. Blumenthal
二维流体中的扩散控制反应：生物膜中脂质横向扩散测量的讨论
DOI：
--
发表时间：
1974
期刊：
影响因子：
--
作者：
K. Naqvi
通讯作者：
K. Naqvi
氧化胆固醇产生有效的免疫抑制作用。
影响因子：
4.4
作者：
G. M. Humphries;H. Mcconnell
通讯作者：
H. Mcconnell