Metabolism of L-Thyroxine by Phagocytosing Human Leukocytes

Intact normal human leukocytes deiodinated L-thyroxine (T₄) with the generation of inorganic iodide, chromatographically immobile origin material, and small quantities of L-triiodothyronine (T₃). When phagocytosis was induced in the leukocytes through the addition of zymosan particles that had been opsonized by coating with plasma, T₄-deiodination was greatly stimulated. In addition to the stimulation of T₄-deiodination, the accumulation by the leukocytes of undegraded T₄ was increased. Anoxia, which has previously been shown not to interfere with phagocytosis, did not prevent the increased cellular accumulation of T₄ that phagocytosis induced, but virtually abolished T₄-deiodination. On the other hand, calcium, which has previously been shown to be required for optimal phagocytosis, was required for the increase in both the cellular accumulation and deiodination of T₄ that phagocytosis induced. Phospholipase-C, which has previously been shown to induce a metabolic burst that mimics that induced by phagocytosis, did not increase the cellular accumulation or deiodination of T₄. On the other hand, colchicine, which has previously been shown to depress the metabolic burst that accompanies phagocytosis, did not prevent the increase in either the cellular accumulation or deiodination of T₄ that phagocytosis induced. Thus, increased accumulation of T₄ by the leukocytes during phagocytosis appears to be the primary factor responsible for the stimulation of deiodination that phagocytosis induces. The increased accumulation of T₄ did not appear to be owing to engulfment of suspending medium surrounding the particles or to binding of T₄ to the particles themselves. In addition to the enhanced cellular accumulation, other factors related to the metabolic burst that accompanies phagocytosis might also be involved in the stimulation of T₄-deiodination. In leukocytes from two patients with chronic granulomatous disease, a disorder in which phagocytosis appears to occur normally but in which the metabolic burst and attendant increase in hydrogen peroxide generation do not occur, stimulation of T₄-deiodination was either greatly diminished or totally lacking. In myeloperoxidase-deficient leukocytes, on the other hand, stimulation of T₄-deiodination was at least as great as that in normal cells. Thus, we conclude that the primary factor responsible for the increased deiodination of T₄ that phagocytosis induces is the enhanced cellular uptake of hormone. The increased generation of hydrogen peroxide that accompanies phagocytosis may be necessary for the enhanced deiodination of the accumulated T₄, but the latter reaction does not require the mediation of myeloperoxidase.

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