ovalbumin and Vascular-Diseases

Rats and guinea pigs were depleted of complement (C') by treatment with heat aggregated human gamma-globulin (agg HGG), zymosan, anti-beta1C globulin, and carrageenan. Although antigen and antibody were bound to vascular structures, Arthus reactions were inhibited. This inhibition was characterized by the lack of C' binding to walls of vessels, the lack of polymorphonuclear (PMN's) cellular infiltrates, and the lack of significant vascular damage. When the same animals were followed for several hours thereafter, levels of serum C' began to rise, C' was bound in tissues, PMN infiltrates appeared, and immunologic vasculitis developed. Blood counts, chemotaxis of PMN's induced by lysates of PMN granules, together with studies on motility and phagocytosis by PMN's obtained from C' depleted rats, failed to establish any abnormality in these cells which would account for inhibition of Arthus reactions. The specificity of C' depletion in terms of effects in the first four reacting components of guinea pig C' was studied. Treatment with agg HGG led to loss of activity in all components, whereas zymosan and anti-beta1C globulin predominately affected the third component (C'3c). Carrageenan mainly affected the first two reacting components of C'. Thus, the availability of the 3c component, or a subsequently reacting component, correlated with the attraction of PMN's to immune reactants in vivo. Various antibodies with different C' fixing capacities in vitro were tested for their ability to induce immunologic vasculitis in normal animals. In rats, only those antibodies which fixed C' in vitro possessed biological activity, whereas in guinea pigs, all antibodies tested, regardless of C' fixation in vitro, induced Arthus reactions. For a given antibody in rats the vasculitis-inducing property was reflected in its ability to bind C' in vascular structures. Rats depleted of circulating PMN's by specific antibody were tested for Arthus activity. Although concentrations of immune reactants and C' were readily detected in vascular structures, no PMN infiltration occurred and significant vascular damage was averted.

Topics: Anaphylaxis; Animals; Antibodies; Arthus Reaction; Carrageenan; Chemotaxis; Chromatography; Complement System Proteins; gamma-Globulins; Guinea Pigs; Immunoelectrophoresis; Neutrophils; Ovalbumin; Pathology; Phagocytosis; Polysaccharides; Rats; Research; Vascular Diseases; Zymosan

Topics: Anaphylaxis; Dextrans; Egg White; Hypersensitivity; Inflammation; Ovalbumin; Pharmacology; Rats; Research; Toxicology; Trypsin Inhibitors; Vascular Diseases

A short term model in which circulating antigen-antibody complexes and host complement localized in vessel walls of guinea pigs was analyzed. Localization was accomplished by subjecting the animals to anaphylactic shock. The circulating macromolecules, such as antigen-antibody complexes, appeared to localize by being trapped in the vessel wall along the basement membrane that acted as a filter during a state of increased permeability of the vessel. It was suggested that this point of localization between the endothelial cell and the basement membrane may well represent the earliest focus of inflammation in diseases caused by the deposition of injurious macromolecules such as soluble antigen-antibody complexes from the blood stream. Complexes localized in the vessel walls did not provoke Arthus-type vasculonecrotic reactions even though in both these vessels and in cutaneous Arthus reactions antibody, antigen, and host complement (C'3c) were deposited in the vessel walls. The possibility was presented that since circulating macromolecules and probably complexes deposited in (a) relatively small amounts, and (b) in a position beneath endothelial cells, they were not strongly chemotactic toward circulating polymorphonuclear leukocytes. Vasculonecrotic reactions, therefore, were not observed. It was brought out that this may be similar to the situation in glomerulonephritis induced by localized immune complexes, in which severe necrosis is not observed. In the Arthus vascular reaction, host complement was found microscopically accumulated with the immune reactants in affected vessel walls.

Topics: Anaphylaxis; Animals; Antibodies; Antigen-Antibody Complex; Antigen-Antibody Reactions; Arthus Reaction; Blood Vessels; Cattle; Complement System Proteins; Electrons; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Guinea Pigs; Immune Sera; Immunoelectrophoresis; Inflammation; Microscopy; Microscopy, Electron; Necrosis; Neutrophils; Ovalbumin; Pathology; Rabbits; Research; Serum Albumin; Serum Albumin, Bovine; Vascular Diseases