Studies on the Mechanism of the Shwartzman Phenomenon

Abstract

The intradermal injection of certain bacterial products in rabbits, followed after a suitable interval of time by the intravenous injection of similar material, results in an intense hemorrhagic-necrotic lesion at the site of the intradermal injection. This phenomenon, first described by Shwartzman (1), may also be produced by an intmdermal injection of a protein antigen in an appropriately sensitized rabbit, followed by an intravenous injection of bacterial products (2). Local infection with certain bacteria or with vaccinia virus also prepares the skin for hemorrhagic necrosis, which can be elicited by the subsequent intravenous injection of bacterial culture filtrates. The phenomenon thus provides a useful laboratory tool for the study of immune reactions occurring in vivo as well as of certain host responses to infectious agents. Numerous investigations of the nature of the phenomenon have been undertaken, but at the present time little is known of the basic mechanisms involved.In an earlier communication, it was shown that a characteristic metabolic abnormality exists in rabbit skin sites prepared for the Shwartzman phenomenon by the intradermal injection of a meningococcal culture filtrate (3). This abnormality consists of a marked degree of aerobic glycolysis, with a consequent local accumulation of lactic acid. It is known that such skin areas contain appreciable numbers of polymorphonuclear leacocytes as a result of the local inflammatory reaction to the bacterial filtrate (4), and it has further been shown that such "exudate leucocytes" exhibited a high degree of aerobic glycosis (5). Because of the difficulty in enumerating the inflammatory cells in Shwartzman-prepared skin sites, however, it was impossible to determine whether the over-all metabolic abnormality could be explained simply on the basis of the leucocyte content.In 1948 Becker (6) reported that the Shwartzman phenomenon could be

Clotting Changes, Including Disseminated Intravascular Coagulation, during Rapid Renal-Homograft Rejection

“…Since the preformed antibodies appear to react with antigens in the transplants, clotting could be induced directly by the antibody-antigen reaction [38][39][40] or by the consequent tissue injury. In addition, antibody-antigen reactions attract polymorphonucleur leukocytes via C′ activation, 41 and these white cells appear capable of inducing clotting 42 and are an important if not essential intermediary in the causation of the thrombosis seen in the local 43 and generalized 42 Shwartzman reactions. Heavy accumulations of polymorphonuclear leukocytes and thrombosis have been seen in man, in whom preformed antibodies induced immediate hyperacute rejections of renal transplants.…”

Platelets and the Shwartzman Phenomenon

“…Furthermore, the Shwartzman phenomenon can be prevented by administration of nitrogen mustard, in doses that produce granulocytopenia but minimal or no thrombocytopenia (2,23).…”

“…Baltimore) PLATES 17 AND 18 (Received for publication, September 10, 1954) There are many indications that the effects of endotoxin upon blood vessels (1), leucocytes (2,3), and coagulation (4)(5) are important in production of the Shwartzman reaction. The effects of endotoxin upon blood vessels and leucocytes cannot be disputed, but involvement of platelets in the intravascular clotting of the Shwartzman phenomenon has never been established with certainty.…”

Role of adhesion glycoproteins CD 18 and intercellular adhesion molecule‐1 in complement‐mediated reactions of rabbit skin

“…Extensive study has revealed much about the processes that underlie the Arthus reaction. The reaction is, as mentioned above, dependent on complement, and can be inhibited by decomplementation with cobra venom factor, anti-complement antibodies or by soluble complement receptors (Stetson & Good, 1951;Humphrey, 1955;Ward & Cochrane, 1965;Cochrane et al, 1970;Cochrane & Janoff, 1974;Rossi et al, 1992). We have previously demonstrated a role for platelet-activating factor Rossi et al, 1992), and for vasodilator prostaglandins in the plasma extravasation associated with the RPA reaction.…”

“…We have previously demonstrated a role for platelet-activating factor Rossi et al, 1992), and for vasodilator prostaglandins in the plasma extravasation associated with the RPA reaction. Neutrophil dependence has been demonstrated by the fact that RPA reactions are suppressed in neutrophil-depleted animals (Stetson & Good, 1951;Humphrey, 1955). …”