Zaidi S I, Singh K P, Raisuddin S, Jafri A, Saxena A K, Choudhary S, Ray P K
Preventive Toxicology Division, Industrial Toxicology Research Centre, M.G. Marg, Lucknow, India.
Immunopharmacol Immunotoxicol. 1995 Nov;17(4):759-73. doi: 10.3109/08923979509037194.
Protein A (PA) is a cell wall glycoprotein of Staphylococcus aureus Cowan I, which possess a number of immunomodulatory and antitumor properties. We have previously shown that PA suppresses the anti-sheep erythrocyte primary antibody response in normal mice. The present investigation evaluates the effect of protein A on the anti-sheep erythrocyte primary antibody response in tumor-bearing mice. The primary antibody response in tumor-bearing mice immunized with sheep red blood cells (SRBC) was suppressed by the intraperitoneal administration of PA in a dose-dependent fashion. The plaque forming cell (PFC) assay was used to assess this response. Maximum suppression of the PFC response was observed at 12 micrograms PA/animal (p < 0.001) and could be observed at doses as low as 1 microgram PA/animal (p < 0.01). The amount of suppression was proportional to the number of PA doses administered. In addition this effect was critically dependent on the timing of PA administration. PA showed no significant effect on PFC when injected after immunization, but it produced pronounced suppression when injected prior to the immunization with SRBC. Maximum suppression of the PFC response was observed when PA was administered one day before the antigen challenge. PA also reduced splenic localization of 51Cr labeled SRBC to 42% (p < 0.01). The altered localization of antigen in spleen may be responsible for reduced PFC response in tumor-bearing mice. Depletion of B-lymphocyte is reported to exhibit tumor inhibition. Therefore, we propose that the suppression of the primary antibody response by PA helps in tumor regression by reducing the soluble immunosuppressive immune complexes.
蛋白A(PA)是金黄色葡萄球菌考恩I型的一种细胞壁糖蛋白,具有多种免疫调节和抗肿瘤特性。我们之前已经表明,PA可抑制正常小鼠对绵羊红细胞的初次抗体反应。本研究评估了蛋白A对荷瘤小鼠抗绵羊红细胞初次抗体反应的影响。腹腔注射PA以剂量依赖的方式抑制了用绵羊红细胞(SRBC)免疫的荷瘤小鼠的初次抗体反应。采用空斑形成细胞(PFC)试验来评估这种反应。在12微克PA/动物时观察到PFC反应的最大抑制(p<0.001),在低至1微克PA/动物的剂量时也可观察到(p<0.01)。抑制程度与给予的PA剂量数成正比。此外,这种效应严重依赖于PA给药的时间。免疫后注射PA对PFC无显著影响,但在SRBC免疫前注射则产生明显抑制。在抗原攻击前一天给予PA时观察到PFC反应的最大抑制。PA还将51Cr标记的SRBC在脾脏中的定位减少到42%(p<0.01)。脾脏中抗原定位的改变可能是荷瘤小鼠PFC反应降低的原因。据报道,B淋巴细胞的耗竭表现出肿瘤抑制作用。因此,我们提出PA对初次抗体反应的抑制通过减少可溶性免疫抑制性免疫复合物有助于肿瘤消退。