STUDY OF THE EFFECTOR MECHANISM INVOLVED IN THE PRODUCTION OF HEMORRHAGIC NECROSIS OF THE SMALL-INTESTINE IN RAT PASSIVE ANAPHYLAXIS

1 The effector mechanism of intestinal necrosis in rat anaphylaxis was studied following several complementary approaches: (i) the use of mo noclonal antibodies (mAb) belonging to different classes (IgG1, IgG2b and IgE anti-DNP), (ii) the assay of mediators, and (iii) the use of p harmacological tools. 2 Lethality and haemorrhagic necrosis of the sma ll intestine were observed in IgE-sensitized rats, whereas IgG mAb pro duced milder physiological disturbances. 3 Inhibition of leukotriene b iosynthesis reduced the drop of systemic blood pressure (BP) and the e xtent of protein-rich plasma exudation but it did not influence the ha emorrhagic component of intestinal necrosis. 4 The antihistamine, pyri lamine, partially diminished the haemorrhagic component of the intesti nal necrosis. 5 The involvement of mediators related to platelet-activ ating factor (PAF) was studied by examining the pharmacological effect s of these autacoids and of PAF-receptor antagonists (PCA4248, UR12460 and BB823). PAF induced intestinal lesions similar to those observed in IgE-sensitized rats and PAF-receptor antagonists markedly decreased haemorrhage in IgE-sensitized rats. 6 PAF levels were transiently inc reased after dinitrophenol (DNP)- bovine serum albumin (BSA) challenge in the small intestine of IgE-sensitized rats. 7 These data stress di fferences in the outcome of anaphylaxis related to the type of recepto rs for the Fc portion of immunoglobulins that are involved. IgE is the antibody class that elicits the most severe response due to the activ ation of mast cells via Fc epsilon RI (surface receptors that bind IgE antibodies with high affinity), and the only one able to produce inte stinal haemorrhagic necrosis. 8 The mast-cell-derived mediators PAF/ac yl-PAF and histamine, most probably associated with tumour necrosis fa ctor alpha/cachectin (TNF-alpha), seem to play a central role in the p roduction of the vascular changes required for the extravasation of er ythrocytes in the small intestine mucosa.