Ertel W, Morrison M H, Ayala A, Chaudry I H
Shock and Trauma Research Laboratories, Michigan State University, East Lansing.
Surgery. 1991 Aug;110(2):440-5; discussion 445-7.
Although hemorrhage depresses macrophage antigen presentation (AP), a critical component in eliciting an antigen-specific immune response, it is not known which particular step in macrophage AP (i.e., uptake, ingestion, catabolism, or presentation of degraded antigens to T cells) is defective. To study this, C3H/HeN mice were bled to an arterial mean blood pressure of 35 mm Hg, maintained for 60 minutes, and then adequately resuscitated. Peritoneal and splenic macrophage cultures were prepared 2 and 24 hours after hemorrhage. Macrophage AP capacity was measured by coculturing macrophages with the T-helper cell clone D10.G4.1. To gain information about macrophage ability to digest the specific antigen conalbumin, lysosomal activity was bypassed by use of chemically denatured conalbumin peptides. To study macrophage ability to present conalbumin peptides, macrophages were fixed and D10.G4.1 proliferation in response to fragmented conalbumin was determined. AP of native conalbumin by peritoneal macrophages and splenic macrophages was depressed (p less than 0.05) by 50% (peritoneal macrophages) and 55% (splenic macrophages) 2 hours and 57% (peritoneal macrophages) and 35% (splenic macrophages) 24 hours after hemorrhage. In contrast, presentation of conalbumin peptides was only slightly decreased. In addition, the ability of fixed peritoneal macrophages and splenic macrophages to present conalbumin peptides was similar in hemorrhaged and sham mice. Because bypassing of macrophage lysosomal activity with degraded native antigens prevented the suppression of AP, the results suggest that hemorrhage-induced suppression of AP is not caused by a reduced macrophage capacity to present antigenic peptides but by decreased antigen catabolism by macrophages.
尽管出血会抑制巨噬细胞抗原呈递（AP），而抗原呈递是引发抗原特异性免疫反应的关键组成部分，但目前尚不清楚巨噬细胞AP的哪个特定步骤（即摄取、吞噬、分解代谢或向T细胞呈递降解抗原）存在缺陷。为了研究这一问题，将C3H/HeN小鼠放血至动脉平均血压为35 mmHg，维持60分钟，然后进行充分复苏。出血后2小时和24小时制备腹膜和脾脏巨噬细胞培养物。通过将巨噬细胞与辅助性T细胞克隆D10.G4.1共培养来测量巨噬细胞的AP能力。为了获取有关巨噬细胞消化特异性抗原伴清蛋白能力的信息，通过使用化学变性的伴清蛋白肽来绕过溶酶体活性。为了研究巨噬细胞呈递伴清蛋白肽的能力，将巨噬细胞固定，并测定D10.G4.1对片段化伴清蛋白的增殖反应。出血后2小时，腹膜巨噬细胞和脾脏巨噬细胞对天然伴清蛋白的AP降低了50%（腹膜巨噬细胞）和55%（脾脏巨噬细胞）（p<0.05），24小时后降低了57%（腹膜巨噬细胞）和35%（脾脏巨噬细胞）。相比之下，伴清蛋白肽的呈递仅略有下降。此外，固定的腹膜巨噬细胞和脾脏巨噬细胞呈递伴清蛋白肽的能力在出血小鼠和假手术小鼠中相似。由于用降解的天然抗原绕过巨噬细胞溶酶体活性可防止AP受到抑制，结果表明出血诱导的AP抑制不是由巨噬细胞呈递抗原肽的能力降低引起的，而是由巨噬细胞抗原分解代谢减少所致。
