Stephan R N, Ayala A, Harkema J M, Dean R E, Border J R, Chaudry I H
Department of Surgery, Michigan State University, East Lansing 48824.
J Surg Res. 1989 Jun;46(6):553-6. doi: 10.1016/0022-4804(89)90019-x.
The mechanism by which simple hemorrhage profoundly impairs the proliferative response of T lymphocytes to mitogen and alloantigen, produces a defect in interleukin-2 generation, and increases the susceptibility to sepsis remains unknown. Since antigen presentation (AP) by the macrophage (M phi) plays a critical role in the antigen-specific activation of T-helper cells and lymphokine production, we investigated whether the function of the M phi as an AP cell is altered following hemorrhage. C3H/HEJ mice were bled to a mean BP of 35 mm Hg, maintained at that level for 1 hr, and then resuscitated. There was no mortality with this model. Control mice were not bled but otherwise treated identically. Immediately after resuscitation the mice were sacrificed and peritoneal M phi (PM phi) as well as splenic adherent cells (SAC) were harvested. AP function was tested by coculturing different numbers of PM phi and SAC with D10.G4.1 cells (2 x 10(4) cells/well) in the presence of conalbumin (300 micrograms/ml). This T-helper cell clone proliferates upon recognition of conalbumin in the context of Iak (a M phi surface membrane glycoprotein), thus directly reflecting M phi AP capability. After 72 hr of incubation, the cultures were pulsed with [3H]thymidine and harvested. D10.G4.1 proliferations induced via AP by PM phi and SAC from hemorrhaged-resuscitated mice were 29 and 24% of control, respectively (P less than 0.05). Thus, we conclude that AP by M phi following hemorrhage is defective despite adequate resuscitation, a mechanism which could explain the state of immunosuppression and enhanced susceptibility to sepsis.
单纯性出血严重损害T淋巴细胞对有丝分裂原和同种异体抗原的增殖反应、导致白细胞介素-2生成缺陷并增加败血症易感性的机制尚不清楚。由于巨噬细胞（M phi）的抗原呈递（AP）在T辅助细胞的抗原特异性激活和淋巴因子产生中起关键作用，我们研究了出血后M phi作为AP细胞的功能是否发生改变。将C3H/HEJ小鼠放血至平均血压35 mmHg，维持该水平1小时，然后进行复苏。该模型无死亡情况。对照小鼠未放血，但其他处理相同。复苏后立即处死小鼠，收集腹腔巨噬细胞（PM phi）以及脾贴壁细胞（SAC）。通过在伴清蛋白（300微克/毫升）存在的情况下将不同数量的PM phi和SAC与D10.G4.1细胞（2×10⁴个细胞/孔）共培养来测试AP功能。该T辅助细胞克隆在识别Iak（一种M phi表面膜糖蛋白）背景下的伴清蛋白时增殖，从而直接反映M phi的AP能力。孵育72小时后，向培养物中加入[³H]胸腺嘧啶核苷并进行收集。出血复苏小鼠的PM phi和SAC通过AP诱导的D10.G4.1增殖分别为对照的29%和24%（P＜0.05）。因此，我们得出结论，尽管进行了充分复苏，但出血后M phi的AP存在缺陷，这一机制可以解释免疫抑制状态和败血症易感性增加的原因。
