Histones Evoke Thymocyte Death in vitro; Histone-Binding Immunoglobulins Decrease Their Cytotoxicity

D. N. Abakushin^*, I. A. Zamulaeva, and A. M. Poverenny

Department of Radiation Biochemistry, Medical Radiological Research Center, Russian Academy of Medical Sciences, ul. Koroleva 4, Obninsk, Kaluga Region, 249020 Russia; fax: (095) 956-1440; E-mail: dna68@yahoo.com or dna@obninsk.su

^* To whom correspondence should be addressed.

Received August 5, 1998

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Effects of various histones, poly-L-lysine, spermine, and the synthetic peptide Arg-Lys-Asn-Val-Tyr-Arg (thymohexine) on intact rat thymocytes were studied. Histones and poly-L-lysine displayed cytotoxicity, causing disorders in the membrane permeability of thymocytes and their death. The dose and time dependences of the effects of histones on thymocytes were determined. Preparations of normal human immunoglobulins bound histones but displayed neither cytotoxicity nor interaction with intact thymocytes. The immunoglobulins significantly decreased the number of dead thymocytes in the presence of total histones. However, the number of cells with detectable immunoglobulin molecules was increased in the presence of histone in the incubation medium. It is suggested that cytotoxicity depends on the number of epitopes on the cell membrane available for interaction with positively charged protein molecules.

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KEY WORDS: cytotoxicity, cell death, histone, thymocytes, antihistone antibodies, natural antibodies

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