A soluble extract from rat spleen, spleen permeability factor (SPF), predominantly protein in content, increases vascular permeability in rat skin by release of histamine and 5-HT from tissue stores. Increase in vascular permeability by SPF is markedly reduced by pretreatment with a combination ofmepyramine and methysergide or by local depletion of skin tissue amines by48/80. SPF releases histamine and 5-HT from rat peritoneal mast cells. This differs from histamine release by antigen, 48/80 and octylamine as it is blocked by 0.1 mM iodoacetic acid and is unaffected by calcium lack or by preheating the cells to 45~ for 5 minutes. There is no detectable kinin release by SPF which is devoid of general proteolytic or TAMe esterolytic activity at neutral pH. Nor does it seem to contain prostaglandins. The possible importance of SPF in the inflammatory response in delayed hypersensitivity reactions is discussed.
1. The effect of bacterial pyrogens on plasma zinc concentration in mice was studied as a method of bioassay for these substances. 2. A dose-related depression of plasma zinc concentrations was observed 4 h after intravenous injection of doses of 0.05-500 ng of purified endotoxins of Salmonella abortus equi, Shigella dysenteriae and Escherichia coli. Responses were dose-dependent and reproducible for each endotoxin in five strains of mice. 3. Tolerance to endotoxin could be induced in mice by injection of doses of 500 ng but was not seen with doses of less than 5 ng, even after repeated treatment. 4. Dinitrophenol, a metabolic inhibitor, and amphetamine, a metabolic enhancer, did not affect plasma zinc levels, indicating that changes in basal metabolic rate do not affect the outcome of this assay. The effects of pyrogenic materials other than endotoxin on plasma zinc levels were also tested and the results suggest that measurement of hypozincaemia in mice provides the basis for a simple, practical and inexpensive test for endotoxins and other pyrogens.
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