Altered Susceptibility In The Chediak-Higashi Syndrome (Aleutian) Mink To The Generalized Shwartzman Reaction

The Aleutian mink is known to have many characteristics similar to other species with Chediak-Higashi Syndrome (CHS) and is considered to have a form of CHS. The CHS mink is partially characterized by defective platelets that lack nucleotide-serotonin dense body storage and by impaired leukocyte function where chemotaxis, degranulation and bacterial killing are decreased. A normalization of CHS leukocyte microbicidal activity in vitro has been demonstrated following the addition of normal platelets. The influence of these platelet-leukocyte defects on the endotoxin induced generalized Shwartzman reaction (GSR) has never previously been examined.

A study was undertaken to determine differences in the endotoxin dose required for GSR induction and in clinical, gross and histopathologic findings in normal and CHS mink. Twenty mink, half normal and half CHS were administered 55:B5 Escherichia coli endotoxin or saline intraperitone- ally followed by a second identical injection 21 hrs. later. Forty-eight hrs. later or at the time of death all animals were necropsied and sampled for histopathologic examination. The results revealed that CHS mink were more susceptible to lethal effects of endotoxin and had different signs and lesions. The dual dosage ranged from 200 μg to 25 mg/kg. CHS mink were symptomatic at 400 μg/kg and were killed at 12.8 mg/kg or greater. Normal mink were symptomatic at 800 μg/kg and died at 25.6 mg/kg. Spleno- hepatomegally with extravasation was present at a dose of 1.6 mg/kg in CHS while it was not a lesion of normal mink or control CHS mink. Renal tubular necrosis was present in CHS mink. Thus, CHS mink were more susceptible to GSR induction which may be the result of CHS platelet/leuko-cyte dysfunction manifest after endotoxin induced vascular injury.