RABBITS IMMUNIZED WITH A PEPTIDE ENCODED FOR BY THE 230-KD BULLOUS PEMPHIGOID ANTIGEN CDNA DEVELOP AN ENHANCED INFLAMMATORY RESPONSE TO UVB IRRADIATION - A POTENTIAL ANIMAL-MODEL FOR BULLOUS PEMPHIGOID
RABBITS IMMUNIZED WITH A PEPTIDE ENCODED FOR BY THE 230-KD BULLOUS PEMPHIGOID ANTIGEN CDNA DEVELOP AN ENHANCED INFLAMMATORY RESPONSE TO UVB IRRADIATION - A POTENTIAL ANIMAL-MODEL FOR BULLOUS PEMPHIGOID
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DOI：
10.1111/1523-1747.ep12358276
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发表时间：
1993-07-01
影响因子：
6.5
通讯作者：
STREILEIN, RD
中科院分区：
文献类型：
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作者：
HALL, RP;MURRAY, JC;STREILEIN, RD
以前尝试开发大疱性类天疱疮（BP）动物模型未能导致皮肤炎症性疾病。P1-2是由230-kD BP抗原cDNA编码的18个氨基酸的肽，其已被证明含有被来自BP患者的循环抗体识别的表位。本研究的目的是确定在用P1-2肽免疫后对兔进行紫外线B照射是否会导致皮肤对该损伤的炎症反应增强。用P1-2或对照肽免疫三只兔。所有用P1-2免疫的兔，和没有对照兔，产生抗P1-2的抗体，其在体外以线性模式在基底膜区结合到人和兔皮肤。用紫外线照射免疫家兔的侧腹。P1-2免疫的家兔对紫外线B照射产生强烈的炎症反应，6 - 9 d后出现表皮坏死和部分部位脱落。对照组家兔仅出现轻度红斑，无脱落，4 - 6 d愈合。P1-2免疫家兔在24 h时的组织学显示真皮-表皮交界处中性粒细胞的炎性浸润，而对照家兔仅显示轻度水肿和稀疏的炎性浸润。所有用P1-2免疫的兔在愈合皮肤的基底膜区都有免疫球蛋白G和C3的线性沉积，而对照组则没有。这些发现表明，针对BP抗原1序列编码的合成肽的抗体可导致兔皮肤上皮损伤后增强的炎症反应。
Previous attempts to develop an animal model of bullous pemphigoid (BP) have failed to result in inflammatory disease in the skin. P1-2 is an 18 - amino acid peptide encoded for by the 230-kD BP antigen cDNA that has been shown to contain an epitope recognized by circulating antibodies from patients with BP. The purpose of this study was to determine if ultraviolet B irradiation of rabbits after immunization with the P1-2 peptide would result in an enhanced inflammatory response in the skin to that injury. Three rabbits were immunized with either P1-2 or a control peptide. All rabbits immunized with P1-2, and none of the control rabbits, developed antibodies against P1-2 that bound in vitro to both human and rabbit skin in a linear pattern at the basement membrane zone. Immunized rabbits were irradiated on the flank with ultraviolet light. Rabbits immunized with P1-2 developed an enhanced inflammatory reaction to ultraviolet B irradiation leading to epidermal necrosis and sloughing of some sites in 6 - 9 d. Control rabbits showed only mild erythema without sloughing, which healed in 4 - 6 d. Histology in the P1-2 immunized rabbits at 24 h revealed an inflammatory infiltrate of neutrophils at the dermal-epidermal junction, whereas control rabbits showed only mild edema and a sparse inflammatory infiltrate. All the rabbits immunized with P1-2 had linear deposits of immunoglobulin G and C3 at the basement membrane zone of healed skin compared to none of the controls. These findings demonstrate that antibodies against a synthetic peptide encoded by the BP antigen 1 sequence can lead to an enhanced inflammatory response after epithelial injury in rabbit skin.