Mak K M, Lieber C S
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, Bronx, New York 10468, USA.
Anat Rec. 2000 Aug 1;259(4):395-404. doi: 10.1002/1097-0185(20000801)259:4<395::AID-AR30>3.0.CO;2-F.
The blood group antigens H, A, B, and Le(b) are oncofetal antigens of the human distal colon. Although these antigens are present in the digestive mucosa of the rat, little is known about their ontogenic expression in the developing rat colon. The present study was undertaken to assess age-dependent and region-related changes of blood group antigens during colonic development and maturation with the aim of determining their fetal phenotype. Antigen expression was assessed by immunohistochemistry using H-, A-, B-, Le(a)-, and Le(b)-specific monoclonal antibodies and formalin-fixed, paraffin-embedded colon sections from fetal, suckling, weanling, and adult rats. Staining of antigen was analyzed with respect to its locations in colonic goblet cells, brush borders, and columnar cells. H, B, and Le(b) antigens were expressed by goblet cells of the distal colon, beginning at 20 days of gestation, but expression was lost from the colon during the first postnatal week, thus exhibiting a fetal phenotype. H and Le(b), but not B, were also expressed by goblet cells of the fetal proximal colon; however, unlike that of the distal colon, their expression increased progressively during postnatal development until adulthood. Fetal phenotypic expression was observed in the brush border of the proximal and distal colon for H antigen, whereas it was observed in that of the distal colon for B antigen. No fetal phenotypic expression of H, B, and Le(b) by columnar cells of the colon was observed. Antigen A was expressed by goblet cells, brush border, and columnar cells of the entire colon at all ages, in concert with the development and maturation of the colon. Therefore, its expression in the rat colon was not fetal in nature. Le(a) was not detected in the colon at any age, except for some sporadic staining in the Golgi zone of columnar cells of the postnatal proximal colon. In conclusion, these data indicate significant age- and region-related changes of blood group antigen expression in the rat colon. Because the fetal phenotypic expression of H, B, and Le(b) by goblet cells of the distal colon mimics that in the human distal colon, the adult rat colon is a potentially useful model for assessing the effects of cocarcinogenic dietary factors, including ethanol, that may induce reexpression of these so-called oncofetal tumor-associated antigens of the colon.
血型抗原H、A、B和Le(b)是人类远端结肠的癌胚抗原。虽然这些抗原存在于大鼠的消化黏膜中，但对于它们在发育中的大鼠结肠中的个体发生表达情况却知之甚少。本研究旨在评估结肠发育和成熟过程中血型抗原随年龄和区域的变化，以确定其胎儿表型。使用H、A、B、Le(a)和Le(b)特异性单克隆抗体，通过免疫组织化学方法对来自胎儿、乳鼠、断奶鼠和成年大鼠的福尔马林固定、石蜡包埋的结肠切片进行抗原表达评估。分析抗原染色在结肠杯状细胞、刷状缘和柱状细胞中的位置。H、B和Le(b)抗原从妊娠20天开始由远端结肠的杯状细胞表达，但在出生后的第一周从结肠中消失，呈现胎儿表型。H和Le(b)，而非B，也由胎儿近端结肠的杯状细胞表达；然而，与远端结肠不同的是，它们的表达在出生后发育过程中逐渐增加直至成年。在近端和远端结肠的刷状缘观察到H抗原的胎儿表型表达，而在远端结肠的刷状缘观察到B抗原的胎儿表型表达。未观察到结肠柱状细胞对H、B和Le(b)的胎儿表型表达。抗原A在所有年龄段的整个结肠的杯状细胞、刷状缘和柱状细胞中均有表达，与结肠的发育和成熟一致。因此，其在大鼠结肠中的表达并非胎儿型。除了在出生后近端结肠柱状细胞的高尔基体区域有一些散在染色外，在任何年龄段的结肠中均未检测到Le(a)。总之，这些数据表明大鼠结肠中血型抗原表达存在显著的年龄和区域相关变化。由于远端结肠杯状细胞对H、B和Le(b)的胎儿表型表达与人类远端结肠相似，成年大鼠结肠是评估包括乙醇在内的可能诱导这些所谓结肠癌胚肿瘤相关抗原重新表达的促癌饮食因素作用的潜在有用模型。
