Ogushi F, Hubbard R C, Fells G A, Casolaro M A, Curiel D T, Brantly M L, Crystal R G
Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.
Am Rev Respir Dis. 1988 Feb;137(2):364-70. doi: 10.1164/ajrccm/137.2.364.
S-type alpha 1-antitrypsin (alpha 1AT) is a deficiency haplotype that differs from the common normal M1 (val213) alpha 1AT haplotype by a single amino acid (glu264 to val264). To evaluate the adequacy of the antineutrophil elastase protection associated with the S homozygous state, alpha 1AT plasma and lung epithelial lining fluid (ELF) levels and antineutrophil elastase function were analyzed in 9 PISS subjects. The plasma alpha 1AT levels of SS subjects were intermediate between that of M1M1 and ZZ subjects (p less than 0.001, all comparisons) and the plasma neutrophil elastase inhibitory capacity paralleled the differences in alpha 1AT concentration (p less than 0.001, all comparisons). The association rate constant for neutrophil elastase of the purified S protein was less than that of the normal molecule (S-type, 7.1 +/- 0.1 X 10(6) M-1 s-1; M1-type, 9.6 +/- 0.2 X 10(6) M-1 s-1; p less than 0.001), but much greater than that for the Z molecule (p less than 0.001). Exposure of the purified S protein to increasing oxidant burdens resulted in a dose-dependent reduction in the ability of the molecule to inhibit neutrophil elastase in a fashion parallel to that of the M1 and Z proteins. Quantification of ELF alpha 1AT levels and antineutrophil elastase capacity demonstrated that the SS ELF parameters were, as in plasma, intermediate between M1 homozygotes and Z homozygotes. Using the association rate constant together with the quantification of ELF alpha 1AT levels, the "in vivo lung inhibition time" was estimated, yielding an assessment of the relative antineutrophil elastase screen of the PISS lower respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS)
S型α1-抗胰蛋白酶（α1AT）是一种缺陷单倍型，它与常见的正常M1（缬氨酸213）α1AT单倍型仅相差一个氨基酸（谷氨酸264变为缬氨酸264）。为评估与S纯合状态相关的抗中性粒细胞弹性蛋白酶保护作用是否充足，对9名PISS受试者的α1AT血浆和肺上皮衬液（ELF）水平以及抗中性粒细胞弹性蛋白酶功能进行了分析。SS受试者的血浆α1AT水平介于M1M1和ZZ受试者之间（p<0.001，所有比较），血浆中性粒细胞弹性蛋白酶抑制能力与α1AT浓度差异平行（p<0.001，所有比较）。纯化的S蛋白对中性粒细胞弹性蛋白酶的结合速率常数低于正常分子（S型，7.1±0.1×10⁶ M⁻¹ s⁻¹；M1型，9.6±0.2×10⁶ M⁻¹ s⁻¹；p<0.001），但远高于Z分子（p<0.001）。将纯化的S蛋白暴露于不断增加的氧化剂负荷下，该分子抑制中性粒细胞弹性蛋白酶的能力呈剂量依赖性降低，其方式与M1和Z蛋白平行。对ELF α1AT水平和抗中性粒细胞弹性蛋白酶能力的定量分析表明，SS的ELF参数与血浆一样，介于M1纯合子和Z纯合子之间。结合结合速率常数和ELF α1AT水平的定量分析，估计了“体内肺抑制时间”，从而对PISS下呼吸道的相对抗中性粒细胞弹性蛋白酶屏障进行了评估。（摘要截短于250字）
