Passage of Native Proteins Through the Normal Gastro-Intestinal Wall 1

Abstract

The view most generally held to-day by the physiologist, chemist and clinician is that undigested antigens are not absorbed through the normal gastro-intestinal wall; and that when such absorption does occur, it is because abnormal or pathological conditions exist, such as stasis, the excessive flooding of the intestines with protein foods, lessened activity of the digestive enzymes, altered conditions of the intestinal mucosa, and greater permeability of the intestinal wall characteristic of new-borns and sucklings. There is some evidence for the absorption of unsplit proteins under normal conditions but this is regarded as a fortuitous occurrence. In the light of the conflicting opinions present in the literature and the important role this subject plays in allergy and other conditions as yet not clearly defined, we determined to reopen the problem. PART I. ANIMAL EXPERIMENTS MethodsGuinea pigs were obtained from a reliable source. They were observed for a week and we used only those which remained healthy and gained in weight. Both young and mature animals were included in order to determine the influence of age. A large number (493) were studied in order to arrive at some approximation of the incidence of this phenomenon under the conditions to be described.We used the anaphylaxis test as the biological method of choice to determine whether native antigens had entered the blood stream from the gastro-intestinal tract. As we have previously shown (1), the Schultz-Dale uterine strip method is less reliable as an index of a state of hypersensitiveness. The difficulties in detecting foreign protein in the blood by precipitin methods are considerable, not only because the material is so greatly diluted, but, as has been frequently shown, because it leaves the blood stream so rapidly.

The Diagnosis and Treatment of Food Allergy

“…Such reactions have been passively transferred by the intracutaneous injection of serum from an allergic individual into the skin of a normal recipient followed by the local injection 24 hours later of the food antigen to which the donor is sensitive (57). Similar local reactions have been reported when the food antigen was administered orally 24 hours after injection of serum into the skin (59). Local reactions similar to those that followed mast cell degranulation in human skin have been reported in vivo after passive sensitization of human ileum and colonic mucosa (34).…”

NEMATODE INDUCED HYPERSENSITIVITY REACTIONS IN GUINEA PIGS: ONSET OF EOSINOPHILIA AND POSITIVE SCHULTZ‐DALE REACTIONS FOLLOWING GRADED INFECTIONS WITH TOXOCARA CANIS

“…Systemic signs suggest that nematode materials are absorbed from the gut into the body, or cause a reaction in the gut which liberates pharmocologic materials. There is evidence that large molecules-including protein-will under certain conditions cross the gut and enter the body of the adult animal (milk protein, horse serum, egg albumin in guinea pigs, Ratner and Gruehl, 1934;Hartley, 1942; diphtheria antitoxin in sheep, Bullen and Batty, 1957;bacterial endotoxin, Ravin and Fine, 1962). Symons and Fairbairn (1962) have shown that Nippostrongylus brasiliensis causes anatomical changes of the gut surface and alteration of certain transport and absorption mechanisms of the gut of infected rats.…”

Paediatric gastrointestinal allergy

“…The permeability of the intestine For allergic reactions to food protein to be initiated one expects that allergen enters the blood stream or at least penetrates the intestinal epithelium and lamina propria which is so rich in immunologically competent cells. The permeability of the gastrointestinal tract has occupied research workers for about 90 years and the early literature is well reviewed by Ratner & Gruehl (1934). The first experiments in this field employed one of three methods:…”