Genovese Arturo, Borgia Guglielmo, Bouvet Jean-Pierre, Detoraki Aikaterini, de Paulis Amato, Piazza Marcello, Marone Gianni
Division of Clinical Immunology and Allergy, University of Naples Federico II, Naples, Italy.
Int Arch Allergy Immunol. 2003 Dec;132(4):336-45. doi: 10.1159/000074901.
Protein Fv, an endogenous protein produced in the liver, is released in biological fluids during viral hepatitis. Acute and chronic viral hepatitis can be associated with cardiovascular derangements. Protein Fv induced the release of histamine, tryptase and the de novo synthesis of prostaglandin D(2) and cysteinyl leukotriene C(4) from mast cells isolated from human heart tissue (HHMC). Protein Fv absorbed with protein A-Sepharose coated with polyclonal IgG did not induce histamine secretion. The maximal percent histamine secretion induced by protein Fv correlated (r(s) = 0.60; p < 0.05) with that induced by anti-IgE, whereas there was no correlation between the release caused by proteins Fv and C5a. Preincubation of HHMC with protein Fv or anti-IgE caused complete cross-desensitization to subsequent challenge with heterologous stimulus. HHMC from which IgE had been dissociated no longer released histamine in response to anti-IgE and protein Fv. A human monoclonal IgE blocked both anti-IgE- and protein Fv-induced release. Three human monoclonal IgM V(H)3(+) inhibited protein-Fv-induced secretion of histamine from HHMC, whereas monoclonal IgM V(H)6(+) did not inhibit the release induced by protein Fv. Protein Fv acts as an endogenous immunoglobulin superantigen by interacting with the V(H)3 domain of IgE to induce the release of mediators from HHMC.
Fv蛋白是肝脏产生的一种内源性蛋白质，在病毒性肝炎期间会释放到生物体液中。急性和慢性病毒性肝炎可能与心血管紊乱有关。Fv蛋白可诱导从人心脏组织分离出的肥大细胞（HHMC）释放组胺、类胰蛋白酶，并从头合成前列腺素D2和半胱氨酰白三烯C4。用包被多克隆IgG的蛋白A-琼脂糖吸附的Fv蛋白不会诱导组胺分泌。Fv蛋白诱导的组胺分泌最大百分比与抗IgE诱导的组胺分泌最大百分比相关（rs = 0.60；p < 0.05），而Fv蛋白和C5a引起的释放之间没有相关性。用Fv蛋白或抗IgE预孵育HHMC会导致对随后异源刺激的完全交叉脱敏。已解离IgE的HHMC不再对抗IgE和Fv蛋白产生组胺释放反应。一种人单克隆IgE可阻断抗IgE和Fv蛋白诱导的释放。三种人单克隆IgM V(H)3(+)可抑制Fv蛋白诱导的HHMC组胺分泌，而单克隆IgM V(H)6(+)则不抑制Fv蛋白诱导的释放。Fv蛋白通过与IgE的V(H)3结构域相互作用，作为一种内源性免疫球蛋白超抗原，诱导HHMC释放介质。
