Lam T M, Whereat N E, Henderson S C, Burgess W H, Shaheen A, Greisler H P
Loyola University Medical Center, Maywood, Illinois.
EXS. 1992;61:346-56. doi: 10.1007/978-3-0348-7001-6_56.
Macrophage/smooth muscle cell interactions play a role in atherogenesis and foreign body reactions to biomaterials. This study investigates the effect of a hypercholesterolemic diet on the ability of smooth muscle cells (SMCs) to respond to monokines which are produced in response to hypercholesterolemia, biomaterials or both. Peritoneal macrophages were harvested from rabbits fed either a normal (M phi NL) or a 2% cholesterol/6% peanut oil diet (M phi ATH) (plasma cholesterol 2840 vs 42.3 [p less than 0.005]). The macrophages were then cultured in the presence of either 1) polyglactin 910 (PG910), 2) Dacron, or 3) no biomaterial (control), and the media collected and pooled by week for the smooth muscle cell mitogenesis assays. Rabbit aortic smooth muscle cells were harvested and cultured from the same two groups of rabbits (SMCNL or SMCATH), quiesced in serum free media (48 h) followed by addition of the test media and 3H-TdR. The addition of either biomaterial to M phi NL-conditioned media increased 3H-TdR incorporation in both smooth muscle lines as compared to controls. PG910 resulted in significantly higher 3H-TdR incorporation than Dacron (weeks 3-5, p less than 0.005). The addition of either biomaterial to M phi ATH also increased 3H-TdR incorporation in both smooth muscle cell lines, however, the magnitude of the response was decreased as compared to the M phi NL-conditioned media in both cell lines (p less than 0.001 for either SMC line). In contrast to the M phi NL-conditioned media, the addition of Dacron to M phi ATH resulted in the highest level of 3H-TdR incorporation in both cell lines as compared to the media without biomaterial. The SMCNL had a higher response to both the monokines in conditioned media (2-fold) and to fetal bovine serum (3-fold) than the SMCATH (p less than 0.001). Although there is a generalized decrease in release of mitogens active on SMCs from M phi ATH, the M phi ATH exposed to Dacron release increased amounts of mitogenic factors, most active on the SMCATH cell line. A common mode of failure of small diameter Dacron grafts in man is pseudointimal hyperplasia, and it is inviting to postulate that the Dacron/macrophage/smooth muscle cell interactions in this atherosclerotic group of patients plays a role in the pathogenesis of this lesion.
巨噬细胞/平滑肌细胞相互作用在动脉粥样硬化形成和生物材料的异物反应中发挥作用。本研究调查了高胆固醇饮食对平滑肌细胞（SMC）响应单核因子能力的影响，这些单核因子是由高胆固醇血症、生物材料或两者共同作用产生的。从喂食正常饮食（M phi NL）或2%胆固醇/6%花生油饮食（M phi ATH）的兔子中采集腹腔巨噬细胞（血浆胆固醇分别为2840和42.3 [p < 0.005]）。然后将巨噬细胞在以下条件下培养：1）聚乳酸910（PG910），2）涤纶，或3）无生物材料（对照），并每周收集培养基并合并用于平滑肌细胞有丝分裂原测定。从相同两组兔子（SMCNL或SMCATH）中采集兔主动脉平滑肌细胞并进行培养，在无血清培养基中静止培养（48小时），随后加入测试培养基和3H - 胸腺嘧啶核苷（3H - TdR）。与对照相比，向M phi NL条件培养基中添加任何一种生物材料均增加了两种平滑肌细胞系中3H - TdR的掺入。PG910导致的3H - TdR掺入量显著高于涤纶（第3 - 5周，p < 0.005）。向M phi ATH中添加任何一种生物材料也增加了两种平滑肌细胞系中3H - TdR的掺入，然而，与两种细胞系中的M phi NL条件培养基相比，反应程度降低（任一SMC系p < 0.001）。与M phi NL条件培养基不同，向M phi ATH中添加涤纶导致两种细胞系中3H - TdR掺入水平最高，与无生物材料的培养基相比。SMCNL对条件培养基中的单核因子（2倍）和胎牛血清（3倍）的反应均高于SMCATH（p < 0.001）。尽管来自M phi ATH的对SMC有活性的有丝分裂原释放普遍减少，但暴露于涤纶的M phi ATH释放出增加量的有丝分裂因子，对SMCATH细胞系活性最强。人类小直径涤纶移植物常见的失效模式是假性内膜增生，因此推测在这组动脉粥样硬化患者中涤纶/巨噬细胞/平滑肌细胞相互作用在该病变的发病机制中起作用。
