Martín M G, Wu S V, Ohning G, Wong H, Walsh J H
Department of Pediatrics, University of California School of Medicine, Los Angeles 90024.
Am J Physiol. 1994 Mar;266(3 Pt 1):G417-24. doi: 10.1152/ajpgi.1994.266.3.G417.
This study demonstrates the effectiveness of parenteral and oral anti-somatostatin monoclonal antibody to stimulate gastrin cell activity in suckling rats. Intraperitoneal anti-somatostatin monoclonal antibody increased serum gastrin concentration (> 2-fold), and orally administered antibodies retained their neutralizing capabilities as demonstrated by a 30% induction of gastrin synthesis. Absorption of luminal monoclonal antibody was time dependent and saturable as demonstrated by measurement of serum murine immunoglobulin G and the subsequent effects on serum gastrin and antral gastrin mRNA concentrations. Enhanced gastrin synthesis after oral administration required whole antibody in that enterally delivered F(ab')2 fragments were not absorbed and did not increase serum gastrin concentrations. In addition, pretreatment with excess Fc fragments decreased monoclonal antibody absorption and eliminated the serum gastrin response to oral monoclonal antibody. These results demonstrate that orally administered murine anti-somatostatin monoclonal antibody was rapidly and efficiently absorbed via an Fc-dependent mechanism and retained immunoneutralizing activity against endogenous somatostatin, neutralizing its inhibition of gastrin cell activity. These results indicate that orally administered monoclonal antibodies could potentially be used to determine the role of other peptides and growth factors as potential physiological regulators during the suckling period of postnatal development.
本研究证明了肠胃外和口服抗生长抑素单克隆抗体在刺激乳鼠胃泌素细胞活性方面的有效性。腹腔注射抗生长抑素单克隆抗体可使血清胃泌素浓度升高(超过2倍),口服抗体仍保持其中和能力,胃泌素合成诱导率达30%即证明了这一点。通过测量血清鼠免疫球蛋白G以及随后对血清胃泌素和胃窦胃泌素mRNA浓度的影响表明,腔内单克隆抗体的吸收具有时间依赖性且可饱和。口服后胃泌素合成增强需要完整抗体,因为经肠道递送的F(ab')2片段未被吸收且未增加血清胃泌素浓度。此外,用过量Fc片段预处理可降低单克隆抗体的吸收,并消除口服单克隆抗体引起的血清胃泌素反应。这些结果表明,口服的鼠抗生长抑素单克隆抗体通过Fc依赖性机制迅速且有效地被吸收,并保留了针对内源性生长抑素的免疫中和活性,中和了其对胃泌素细胞活性的抑制作用。这些结果表明,口服单克隆抗体可能可用于确定其他肽和生长因子在出生后发育的哺乳期作为潜在生理调节剂的作用。