EFFECTS OF INFLAMMATORY CYTOKINES AND PHORBOL ESTERS ON THE ADHESION OF U937 CELLS, A HUMAN MONOCYTE-LIKE CELL-LINE, TO ENDOTHELIAL-CELL MONOLAYERS AND EXTRACELLULAR-MATRIX PROTEINS
EFFECTS OF INFLAMMATORY CYTOKINES AND PHORBOL ESTERS ON THE ADHESION OF U937 CELLS, A HUMAN MONOCYTE-LIKE CELL-LINE, TO ENDOTHELIAL-CELL MONOLAYERS AND EXTRACELLULAR-MATRIX PROTEINS
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DOI：
10.1002/jlb.49.6.566
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发表时间：
1991-06-01
影响因子：
5.5
通讯作者：
WELKOVICH, L
中科院分区：
文献类型：
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作者：
CAVENDER, DE;EDELBAUM, D;WELKOVICH, L
单核吞噬细胞在慢性炎症部位的积聚依赖于血液传播的单核细胞通过血管内皮细胞外渗到结缔组织中的速率的增加。 一旦单核细胞迁移到结缔组织中，它们可能分化成组织巨噬细胞，推测是在与细胞外基质蛋白相互作用之后。 为了研究这些过程，我们测试了细胞因子和佛波酯对U937细胞（一种人单核细胞样细胞系）与培养的内皮细胞（EC）和基质蛋白粘附的影响。 在没有细胞因子的情况下，非常少的U937细胞粘附于EC（在大多数实验中为5%或更少）。 当EC用重组白细胞介素-1-α（IL-1-alpha）、IL-1-β、肿瘤坏死因子-α（TNF-α）或光毒素（LT;也称为TNF-β）预处理最佳时间段（4-8小时）时，35-85%的U937细胞能够结合。 干扰素-γ（IFN-γ）和白细胞介素-2（IL-2）不刺激U937-EC结合，即使IFN-γ显示增加T淋巴细胞的EC结合。 佛波酯也极大地刺激U937-EC粘附，但在这种情况下，这种增加是由于对U937细胞的作用。 单克隆抗体（MAb），60.3，对白细胞粘附分子的CD 11/CD 18家族的部分抑制未处理和佛波酯处理的U937细胞的粘附non-cytokine处理的EC。 然而，该MAb对U937细胞与TNF-α处理的EC的结合没有影响。 因此，U937细胞利用CD 11/CD 18依赖性和非依赖性机制来粘附EC。 在没有刺激剂的情况下，只有一小部分U937细胞（2-20%）粘附到纤连蛋白（FN），几乎没有结合到层粘连蛋白（LN）或明胶（变性I型胶原）。 在佛波醇酯的存在下，更大比例的U937细胞粘附于FN，与LN或明胶结合的细胞比例仅略有增加。 在含有氨基酸序列arg-gly-asp（RGD）的五肽（其是FN的细胞结合结构域之一的一部分）存在下进行的另外的粘附测定证明，含有RGD的肽几乎完全阻断佛波酯诱导的U937细胞与FN的粘附。 相反，该肽对佛波酯诱导的U937细胞与EC的结合没有抑制作用。
The accumulation of mononuclear phagocytes at sites of chronic inflammation is dependent on an increase in the rate of extravasation of blood-borne monocytes through the vascular endothelium into the connective tissue. Once the monocytes have emigrated into the connective tissue, they may differentiate into tissue macrophages, presumably following interactions with extracellular matrix proteins. To study these processes, we tested the effects of cytokines and phorbol esters on the adhesion of U937 cells, a human monocyte-like cell line, to cultured endothelial cells (EC) and to matrix proteins. In the absence of cytokines, very few of the U937 cells adhered to EC (5% or less in most experiments). When EC were pretreated for optimal periods of time (4-8 hr) with recombinant interleukin-1-alpha (IL-1-alpha), IL-1-beta, tumor necrosis factor-alpha (TNF-alpha), or lymphotoxin (LT; also known as TNF-beta), 35-85% of the U937 cells were able to bind. Interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) did not stimulate U937-EC binding, even though IFN-gamma was shown to increase EC adhesiveness for T lymphocytes. Phorbol esters also greatly stimulated U937-EC adhesion but, in this case, the increase was due to an action on the U937 cells. A monoclonal antibody (MAb), 60.3, against the CD11/CD18 family of leukocyte adhesion molecules partially inhibited the adhesion of untreated and phorbol ester-treated U937 cells to noncytokine-treated EC. However, that MAb had no effect on U937 cell binding to TNF-alpha-treated EC. Thus U937 cells use both CD11/CD18-dependent and -independent mechanisms to adhere to EC. In the absence of stimulating agents, only a small proportion of the U937 cells (2-20%) adhered to fibronectin (FN), and almost none bound to either laminin (LN) or gelatin (denatured type I collagen). In the presence of phorbol esters, a much larger proportion of the U937 cells adhered to FN, with only slight increases in the proportion of cells which bound to LN or gelatin. Additional adhesion assays performed in the presence of a pentapeptide containing the amino acid sequence arg-gly-asp (RGD), which is part of one of the cell-binding domains of FN, demonstrated that the RGD-containing peptide almost totally blocked the phorbol ester-induced adhesion of U937 cells to FN. In contrast, the peptide had no inhibitory effect on the phorbol ester-induced binding of U937 cells to EC.