Roman-Franco A A, Santiago-Delpin E A
Med Hypotheses. 1977 Nov-Dec;3(6):235-40. doi: 10.1016/0306-9877(77)90030-5.
Membrane lipids play an important role in cellular responses to exogenous signals. In immunocompetent lymphocytes, marked changes in the concentrations of membrane lipids occur following cell-antigen interaction. These changes lead to an increase in membrane fluidity, thus facilitating the microaggregation of receptor-antigen complexes. This event constitutes the inductive signal for lymphocytes. Lipid profile alterations leading to increased concentration of membrane cholesterol, of polyunsaturated lipids, or of both, bring about a decrease in membrane fluidity. The latter interferes with receptor displacement preventing delivery of an inductive signal to the responding cell. Interference with microaggregation is readily brought about in interactions involving low affinity antigens, such as tumoral antigens. We postulate that in hyperlipidemic and hypercholesterolemic states there is decreased immune responsiveness to weak antigens due to the aformentioned lipid profile alterations in the membranes of immunocompetent cells. The manner in which an increase in the concentration of the lipids mentioned can lead to decreased immune responsiveness and hence to an increased incidence of malignancies in hyperlipidemic and hypercholesterolemic states is the hypothesis presented in this paper.
膜脂在细胞对外源信号的反应中起重要作用。在具有免疫活性的淋巴细胞中，细胞与抗原相互作用后，膜脂浓度会发生显著变化。这些变化导致膜流动性增加，从而促进受体 - 抗原复合物的微聚集。这一事件构成淋巴细胞的诱导信号。导致膜胆固醇、多不饱和脂质或两者浓度增加的脂质谱改变会使膜流动性降低。后者会干扰受体移位，阻止向反应细胞传递诱导信号。在涉及低亲和力抗原（如肿瘤抗原）的相互作用中，很容易对微聚集产生干扰。我们推测，在高脂血症和高胆固醇血症状态下，由于上述免疫活性细胞膜脂质谱的改变，对弱抗原的免疫反应性降低。本文提出的假设是，上述脂质浓度的增加导致免疫反应性降低，进而导致高脂血症和高胆固醇血症状态下恶性肿瘤发病率增加的方式。
