서지주요정보
Histone-mediated innate defense system in vertebrate = 고등동물에서 Histone에 의한 생체방어기작
서명 / 저자 Histone-mediated innate defense system in vertebrate = 고등동물에서 Histone에 의한 생체방어기작 / Hun-Sik Kim.
저자명 Kim, Hun-Sik ; 김헌식
발행사항 [대전 : 한국과학기술원, 2001].
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8012195

소장위치/청구기호

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DBS 01009

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초록정보

The intestinal epithelium forms a first line of innate host defense by secretion of proteins with antimicrobial activity against microbial infection. Despite the extensive studies on the antimicrobial host defense in many gastrointestinal tracts, little is known on the antimicrobial defense system of a stomach. The potent antimicrobial peptide buforin I consisting of 39 amino acids was isolated recently from the stomach tissue of an Asian toad, Bufo bufo gargarizans. In this study I examined the mechanism of buforin I production in the toad stomach tissue. Buforin I is produced by the action of pepsin isozymes, named pepsin Ca and Cb, cleaving the Tyr39-Ala40 bond of histone H2A. Immunohistochemical analysis revealed that buforin I is present extracellularly on the mucosal surface, and unacetylated histone H2A, a precursor of buforin I, is localized in the cytoplasm of gastric gland cells. Furthermore, Western blot analysis showed that buforin I is also present in the gastric fluids, and immunoelectron microscopy detected the localization of the unacetylated histone H2A in the cytoplasmic granules of gastric gland cells. The distinct subcellular distribution of the unacetylated histone H2A and the detection of the unacetylated buforin I both on the mucosal surface and in the lumen suggest that buforin I is produced from the cytoplasmic unacetylated histone H2A secreted into the gastric lumen and subsequently processed by pepsins. My results indicate that buforin I along with pepsins in the vertebrate stomach may contribute to the innate host defense of the stomach against invading microorganisms. Colonization and infection of placental tissues often lead to adverse pregnancy outcomes such as preterm birth, a leading cause of neonatal morbidity and mortality. The fetal membranes of placenta, a physical and active barrier to microbial invasion, encapsulate the fetus and secure its intrauterine environment. In this study I have shown that histone proteins may constitute one of important innate defense systems with antimicrobial and endotoxin-neutralizing activities in fetal membranes of human placenta during pregnancy. Two salt-resistant antimicrobial proteins were purified to homogeneity using heparin-affinity and reverse-phase high-performance liquid chromatography. Characterization of these proteins revealed that they are identical to histone H2B and H2A, respectively. Moreover, histone H2B and H2A showed dose-dependent inhibition of endotoxin activity of lipopolysaccharide (LPS) by binding and blocking both the core and lipid A moiety of LPS. Consistent with a role for the histones in the establishment of placental innate defense, histone H2B and H2A were highly expressed in the cytoplasm of syncytiotrophoblast and aminon, where they were localized mainly to the epithelial surface. Culturing of amnion-derived WISH cells led to the constitutive release of histone H2B. My studies suggest that histone H2B and H2A may endow the epithelium of placenta with barrier function of antimicrobial and endotoxin-neutralizing potential against invading microorganisms in this immune privileged site.

본 연구의 결과로 강력한 항균펩타이드인 buforin I 이 두꺼비 위 분비세포의 세포질 과립에서 분비된 unacetylated histone H2A로부터 pepsin C isozyme의 작용에 의해 생성됨을 보였다. Buforin I 은 위액뿐만 아니라 위상피세포의 mucosal surface에 존재하였다. 이러한 buforin I 의 위내 분포는 mucosal immune cell들과 더불어 위상피세포의 방어기능을 유지하는데 기여를 할 수 있다. 따라서 본 결과들은 buforin I 같은 항균펩타이드들이 위산액과 더불어 작용하여 위와 말단 소장기관의 생체방어 기작에 기여함을 의미한다. 이상의 결과를 바탕으로 histone 단백질에 의한 생체방어 기작이 고등동물의 위뿐만 아니라 다른 조직에서도 작용하는 지를 연구하였다. 이를 위해 유전적으로 이형인 태아가 정상적으로 성장될 수 있게 모체의 면역력이 저하되어 병원균에 대한 감염위험성이 높은 태반을 선택하였다. 본 연구결과 사람태반에서 분리된 histone H2B와 H2A가 salt-resistant 항균력을 가지며 병원균 독소에 대한 중화활성을 가짐을 보였다. 또한 이들이 사람태반에서 외부 병원균 침입에 대한 방어기능을 수행함을 확인하였다. 이상의 결과들로부터 외부의 병원균에 쉽게 노출된 소화기계와 태반 조직에 기존에 알려지지 않은 histone에 의해 매개되는 중요한 생체방어 기작이 존재함을 확인하였다.

서지기타정보

서지기타정보
청구기호 {DBS 01009
형태사항 vii, 88 p. : 삽도 ; 26 cm
언어 영어
일반주기 저자명의 한글표기 : 김헌식
지도교수의 영문표기 : Sun-Chang Kim
지도교수의 한글표기 : 김선창
수록잡지명 : "Pepsin-mediated processing of the cytoplasmic histone H2A to strong antimicrobial peptide buforin I". The journal of immunology, v.165 no.6, pp. 3268-3274 (2000)
수록잡지명 : "Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions. ". Biochemical and biophysical research communications, v.244 no.1, pp. 253-257 (1998)
학위논문 학위논문(박사) - 한국과학기술원 : 생물과학과,
서지주기 Reference : p. 70-88
주제 Vertebrate
Innate defense system
Antimicrobial protein
Histone
고등동물
생체방어기작
항균단백질
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