Ohkuni Hisashi, Todome Yuko, Watanabe Yukino, Ishikaw Toshio, Takahashi Hidemi, Kannari Yutaka, Kato Hidehito, Uchiyama Takehiko, Saito Hirohisa, Fischetti Vincent A, Zabriskie John B
Clinical Lab, Medca Japan Co. Ltd, Saitama, Tokyo, Japan.
Indian J Med Res. 2004 May;119 Suppl:33-6.
BACKGROUND & OBJECTIVES: Streptococcal pyrogenic exotoxin B/streptococcal cysteine protease (SPE B/SCP) is considered to be one of the virulence factors of Streptococcus pyogenes (S. pyogenes) which causes serious diseases such as severe invasive infections and streptococcal toxic shock syndrome (STSS). There are no reports on the histamine releasing activity of SPE B/SCP from mast cells, although several biological activities have been studied. It is not clear whether SPE B/SCP have the superantigenic activity. We studied whether SPE B/SCP plays as a pathogenic factor in streptococcal infections and STSS through a histamine releasing activity.
Human mast cells and basophils were generated from CD34 positive cells isolated from cord blood and cultured in the presence of rIL-6, stem cell factor and/or rIL-3. The capacity of increasing capillary permeability of recombinant SPE B/SCP (rSPE B/SCP) was studied by using the skin of guinea pigs. Mitogenic activity to human T-cells of rSPE B/SCP was studied by incorporation of (3)Hthymidine. The levels of histamine in the plasma of patients with STSS and controls were measured by ELISA kit.
rSPE B/SCP induced increased capillary permeability in the skin of guinea pigs, but both SPE A and SPE C did not exhibit such activity. Histamine was released from cultured human mast cells stimulated with rSPE B/SCP. The rSPE B/SCP did not exhibit mitogenic activity to human T-cells. Three of the 7 patients with STSS showed higher levels of plasma histamine than those of normal subjects.
INTERPRETATION & CONCLUSION: The results suggested that increased capillary permeability and histamine release from mast cells induced by rSPE B/SCP might be involved in STSS and/or streptococcal infection of skin and mucous membrane.
化脓性链球菌致热外毒素B/链球菌半胱氨酸蛋白酶（SPE B/SCP）被认为是化脓性链球菌（A组链球菌）的致病因素之一，可引发严重疾病，如严重侵袭性感染和链球菌中毒性休克综合征（STSS）。尽管已对其多种生物学活性进行了研究，但关于SPE B/SCP对肥大细胞组胺释放活性的报道尚未见。目前尚不清楚SPE B/SCP是否具有超抗原活性。我们通过组胺释放活性研究了SPE B/SCP在链球菌感染和STSS中是否作为致病因素起作用。
从脐血分离的CD34阳性细胞中培养生成人肥大细胞和嗜碱性粒细胞，并在重组白细胞介素-6（rIL-6）、干细胞因子和/或重组白细胞介素-3（rIL-3）存在的条件下进行培养。采用豚鼠皮肤研究重组SPE B/SCP（rSPE B/SCP）增加毛细血管通透性的能力。通过掺入（3）H胸腺嘧啶核苷研究rSPE B/SCP对人T细胞的促有丝分裂活性。采用酶联免疫吸附测定试剂盒（ELISA试剂盒）检测STSS患者和对照组血浆中的组胺水平。
rSPE B/SCP可使豚鼠皮肤的毛细血管通透性增加，但SPE A和SPE C均未表现出此类活性。rSPE B/SCP刺激培养的人肥大细胞可释放组胺。rSPE B/SCP对人T细胞未表现出促有丝分裂活性。7例STSS患者中有3例血浆组胺水平高于正常受试者。
结果表明，rSPE B/SCP诱导的毛细血管通透性增加和肥大细胞组胺释放可能与STSS和/或皮肤及黏膜的链球菌感染有关。
