Role of neutrophils in gastric damage induced by platelet activating factor.
Platelet-activating factor (PAF) has recently been shown to be a potent ulcerogenic agent in the stomach and intestinal mucosa. Its extract mechanism of action is not yet known although histological studies suggest that vasocongestion is an important feature of PAF-induced damage. We have therefore studied the activity of various agents with different modes of action toward PAF-induced gastrointestinal lesions in the rat (PAF 2 micrograms/kg i.v.; macroscopic lesions of tissue scored 20 min later; arbitrary scale from 0 to 4). Drugs were administered either i.m., s.c. (5 min) or orally (30 min) before PAF injection. PAF-induced gastric lesions were strongly inhibited by the natural PAF-antagonist BN 52021 as well as by atropine sulphate and cimetidine which implicates cholinergic stimulation in the ulcerogenic activity of PAF. The somatostatin analog BIM 23014 was also very potent against PAF, perhaps by reducing the parasympathetic stimulation in the gastric wall as described for somatostatin. Allopurinol, which is a free radical scavenger also almost totally inhibited PAF-induced gastric damage, suggesting that neutrophils are involved in the mucosal lesions. The considerable inhibition of the gastric effects of PAF found in neutrophil-depleted animal supports this hypothesis. Theophylline and disodium cromoglycate, mast cell stabilizing drugs which were also active in our model, could act by protecting mast cell degranulation induced by free radicals released from activated neutrophils. A multifunctional process seems to determine the mucosal gastric damage induced by PAF, but parasympathetic stimulation and neutrophil activation play a major role in this pathology.
Etienne
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Institut Henri Beaufour Research Laboratories, ZA de Courtaboeuf, Les Ulis, France.
Thonier
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Hecquet
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Braquet
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D000818:Animals; D005753:Gastric Mucosa / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology
D010972:Platelet Activating Factor