Lee D G, Cho B H, Hervey J, Daynes R A
Department of Pathology, University of Utah Medical School, Salt Lake City 84132.
Reg Immunol. 1988 Nov-Dec;1(3):149-62.
Studies were undertaken to evaluate factors capable of influencing the intensity of contact hypersensitivity (CH) and delayed-type hypersensitivity (DTH) responses in mice. It is well known that the exposure of animals to ultraviolet radiation (UVR) causes a depression of CH and DTH responses whereas the injection of mice with nanogram quantities of pertussis toxin (PT) before sensitization results in greatly augmented CH responses following hapten challenge. Histopathology and biochemical quantitation of myeloperoxidase (MPO) activity in biopsies obtained from the challenged ears from normal, UVR-exposed, or PT-treated animals determined that a direct correlation existed between the intensity of the ear-swelling response and the degree of neutrophil infiltrate into the challenge site. Few neutrophils were observed to infiltrate into the ears of UVR-exposed animals when compared to normal animals, whereas a pronounced neutrophil infiltration was observed in the challenged ears of PT-pretreated animals. These observations led us to question whether tissue-infiltrating neutrophils, or their products, might be involved in controlling the intensity of CH and DTH responses. The direct injection of murine neutrophils, neutrophil homogenates, and a neutrophil granular fraction into the ear pinnae of normal mice resulted in a dosage-dependent ear-swelling reaction after 24 hours that was histologically similar to antigen-induced CH or DTH responses (primarily mononuclear cell infiltrate). Additional studies determined that an injection of elastase, collagenase, or peptides of elastin or collagen generated by elastase or collagenase treatment of insoluble elastin or collagen also caused a pronounced ear-swelling accompanied by a mononuclear cell infiltration. On the basis of these studies, coupled to experiments that demonstrated an inhibitory influence of alpha-1-antitrypsin (alpha 1-AT) on CH and DTH responses, we propose that neutrophil proteases may play an important role in regulating the intensity of CH and DTH responses in mice through their capacity to degrade extracellular matrix proteins whose peptide fragments are chemotactic for mononuclear cells and fibroblasts.
开展了多项研究以评估能够影响小鼠接触性超敏反应（CH）和迟发型超敏反应（DTH）强度的因素。众所周知，动物暴露于紫外线辐射（UVR）会导致CH和DTH反应受到抑制，而在致敏前给小鼠注射纳克量的百日咳毒素（PT）会使在受到半抗原攻击后CH反应大幅增强。对正常、UVR暴露或PT处理动物的受试耳部活检组织进行组织病理学检查和髓过氧化物酶（MPO）活性的生化定量分析后发现，耳部肿胀反应的强度与中性粒细胞浸润到攻击部位的程度之间存在直接相关性。与正常动物相比，在UVR暴露动物的耳部几乎未观察到中性粒细胞浸润，而在PT预处理动物的受试耳部则观察到明显的中性粒细胞浸润。这些观察结果促使我们质疑组织浸润的中性粒细胞或其产物是否可能参与控制CH和DTH反应的强度。将小鼠中性粒细胞、中性粒细胞匀浆和中性粒细胞颗粒组分直接注射到正常小鼠的耳廓中，24小时后会产生剂量依赖性的耳部肿胀反应，从组织学上看，这与抗原诱导的CH或DTH反应（主要是单核细胞浸润）相似。进一步的研究确定，注射弹性蛋白酶、胶原酶或由弹性蛋白酶或胶原酶处理不溶性弹性蛋白或胶原蛋白产生的弹性蛋白或胶原蛋白肽也会导致明显的耳部肿胀，并伴有单核细胞浸润。基于这些研究，再结合那些证明α-1抗胰蛋白酶（α1-AT）对CH和DTH反应具有抑制作用的实验，我们提出中性粒细胞蛋白酶可能通过其降解细胞外基质蛋白的能力在调节小鼠CH和DTH反应强度方面发挥重要作用，这些细胞外基质蛋白的肽片段对单核细胞和成纤维细胞具有趋化作用。
