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The extravascular nature of arthus reactions elicited by ferritin. A combined light and electron microscopic analysis of immune states in rabbit ear chambers and mesenteries

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Summary

Rabbits were immunized with ferritin and were challenged with the antigen (1) by placing the ferritin on top of rabbit ear chamber tissue and (2) by placing it on top of immune mesentery. In immune animals, a brisk and mounting reaction was characterized by white blood cell sticking and emigration, thrombosis, stasis, vessel shutdown and necrosis. Electron micrographs of tissue taken from sites of injury revealed aggregates of electrondense material with a double density. The material appeared in the extravascular tissue, often perivascularly, inside and outside of white blood cells, the cells being virtually exclusively polymorphonuclear leucocytes. The clumps, presumably antigen-antibody complexes, were never found intraluminally. Ferritin was not found phagocytized by endothelial cytoplasm.

The evidence permits the hypothesis that such reactions have their genesis in the extravascular deposition of immune complexes, not in the vessel wall as many observers have held.

It is possible, however, that this may be a property of electron-dense high molecular antigens, such as ferritin, and not necessarily a general characteristic of reactions associated with hypersensitivity states of the Arthus type or of other types.

It is the purpose of this communication to present the evidence that in the genesis of the Arthus reaction, the site for the reactants is in the extravascular tissue, not in the vessel wall. Subsequently, blood vessel injury occurs and, with it, the exudative phase of the reaction. This does not diminish the importance of the polymorphonuclear leucocyte in the reaction but, in perspective, it identifies white cell sticking and emigration, and endothelial injury, as relatively late events in the phenomenon. The evidence suggests that the early events of the Arthus reaction may involve white blood cells that have emigrated across capillary beds and are present in extravascular tissue before the stimulus provided by immune reactants. Such an hypothesis offers a unifying concept for the phenomenon and, if valid, explains many of the apparently disparate experimental facts surrounding the Arthus reaction.

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Authors and Affiliations

  1. Departments of Medicine, Anatomy and Pathology, New York University School of Medicine, USA

    Lester Grant, Michael H. Ross, John Moses, Philip Prose, Benjamin W. Zweifach & Robert H. Ebert

  2. Department of Medicine, Harvard Medical School, USA

    Lester Grant, Michael H. Ross, John Moses, Philip Prose, Benjamin W. Zweifach & Robert H. Ebert

  3. The Medical Service (Infectious Disease Unit), Massachusetts General Hospital, Boston, USA

    Lester Grant, Michael H. Ross, John Moses, Philip Prose, Benjamin W. Zweifach & Robert H. Ebert

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  1. Lester Grant
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  2. Michael H. Ross
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  3. John Moses
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  4. Philip Prose
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  5. Benjamin W. Zweifach
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  6. Robert H. Ebert
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This work was supported in part by USPHS Grant Nos. AM 05071, 05433, 08771 and 4501, the John Hartford Foundation, and the Health Research Council of New York City. — We would like to acknowledge the superior technical assistance of Mrs. Francine Hu, Mrs. Jeanette Scott, Paul Kasnitz, M. D., Michael Napoliello, M. D., Carl Nathan and Miss Tana Meyer, and the many useful suggestions and critical eye of Dr. Lewis Thomas, Dean of the New York University School of Medicine, during the course of the experiments. We are grateful for the many courtesies and generous assistance provided by Dr. William S. Tillett, Professor of Medicine, Emeritus, New York University School of Medicine. We are indebted to Drs. H. Sherwood Lawrence and Jonathan Uhr of the Department of Medicine, for helpful suggestions in reviewing the manuscript.

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Grant, L., Ross, M.H., Moses, J. et al. The extravascular nature of arthus reactions elicited by ferritin. A combined light and electron microscopic analysis of immune states in rabbit ear chambers and mesenteries. Z. Zellforsch. 77, 554–588 (1967). https://doi.org/10.1007/BF00319348

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