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Selenium Deficiency Alters the Lipoxygenase Pathway and Mitogenic Response in Bovine Lymphocytes^1,2,

Departments of Veterinary Science ^* Molecular and Cell Biology, The Pennsylvania State University, University Park, PA 16802

We investigated the effect of altered selenium (Se) nutrition on arachidonic acid oxidation in immune cells. Experiments were conducted with peripheral blood lymphocytes obtained from dairy cattle fed diets either supplemented with or deficient in Se. The results indicate that the concanavalin A-stimulated lymphocyte proliferation was significantly lower in Se-deficient cows. When stimulated by calcium ionophore A23187, the lymphocytes derived from Se-deficient cows produced significantly less 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B₄ (LTB₄) than those obtained from Se-supplemented cows. When included in cell cultures from animals fed +Se diets, 5-HETE and LTB₄ elicited a partial reversal of the inhibition of lymphocyte proliferation by either hydrocortisone or nordihydroguaiaretic acid. Based on this information, we postulate that dietary Se status, which in turn determines tissue Se concentration, plays an important role in the regulation of arachidonate metabolism by way of the 5-lipoxygenase pathway. This may be one of the biochemical mechanisms underlying the inhibition of lymphocyte proliferation and the decrease in resistance to infectious diseases observed in Se-deficient animals.

KEY WORDS: • lipoxygenase pathway • eicosanoids • lymphocyte proliferation • bovine • selenium deficiency

¹ Presented in part at the Annual Meeting of the Federation of American Societies for Experimental Biology, April 1991, Atlanta, GA [Cao, Y-Z, Mastro, A. M., Scholz, R. W., Hildenbrandt, G. & Reddy, C. C. (1991) Effects of altered selenium nutrition on lymphocyte proliferation: the role of lipoxygenase products. FASEB J. 5: 1757 (abs.)].

² Supported by the National Institutes of Health (HL 31245 and CA 24385) and the Pennsylvania Department of Agriculture.

³ To whom correspondence should be addressed.

Manuscript received 11 May 1992. Revision accepted 7 July 1992.