The influence of macrophage depletion on ligament healing.
The influence of macrophage depletion on ligament healing.
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DOI：
10.3109/03008207.2010.511355
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发表时间：
2011-06
影响因子：
2.9
通讯作者：
Vanderby R
中科院分区：
文献类型：
--
作者：
Chamberlain CS;Leiferman EM;Frisch KE;Wang S;Yang X;van Rooijen N;Baer GS;Brickson SL;Vanderby R
尽管细胞事件的复杂级联重建受损的细胞外基质，韧带愈合导致机械性较差的瘢痕样组织。在正常愈合过程中，伤口部位内巨噬细胞的数量显著增加。然后，肉芽组织扩展到任何残留的正常韧带组织（爬行替代），导致更大的愈合区域，更大的机械损害和低效的修复过程。为了研究巨噬细胞对修复过程的影响，大鼠接受了双侧内侧副韧带的手术断裂。治疗动物在破裂前2天接受脂质体包封的氯膦酸盐以消融吞噬巨噬细胞。然后在第5、11和28天收集韧带用于免疫组织化学和/或机械测试。氯膦酸盐治疗在第5天减少了M1和M2巨噬细胞，并改变了早期愈合。然而，巨噬细胞在第5天后有效地恢复到对照水平，并重新启动伤口愈合反应。我们的研究结果表明，早期巨噬细胞反应，这是必要的清创损伤组织的伤口，也是重要的细胞因子释放介导正常的修复过程。此外，巨噬细胞的非特异性抑制（不考虑特定的巨噬细胞群体）可以控制过度的肉芽组织形成，但对早期基质形成和韧带强度有害。
Despite a complex cascade of cellular events to reconstruct damaged extracellular matrix, ligament healing results in a mechanically inferior, scar-like tissue. During normal healing the number of macrophages significantly increases within the wound site. Then, granulation tissue expands into any residual, normal ligamentous tissue (creeping substitution), resulting in a larger region of healing, greater mechanical compromise, and an inefficient repair process. To study the effects of macrophages on the repair process, rats underwent bilateral, surgical rupture of their medial collateral ligaments. Treatment animals received liposome-encapsulated clodronate 2 days before rupture to ablate phagocytosing macrophages. Ligaments were then collected at day 5, 11, and 28 for immunohistochemistry and/or mechanical testing. Clodronate treatment reduced both the M1 and M2 macrophages at day 5 and altered early healing. However, the macrophages effectively returned to control levels after day 5 and reinitiated a wound healing response. Our results suggest that an early macrophage response, which is necessary for debridement of damaged tissue in the wound, is also important for cytokine release to mediate normal repair processes. Additionally, non-specific inhibition of macrophages (without regard to specific macrophage populations) can control excessive granulation tissue formation but is detrimental to early matrix formation and ligament strength.