Inhibition of metabolic activity of polymorphonuclear granulocytes by thyroid stimulating antibodies

Abstract

Both thyrocytes and polymorphonuclear granulocytes (PMNs) are known to have on their surface thyrotropin receptor (TSH-R). Anti-TSH-R antibodies having stimulating and blocking effects on thyroid function have been detected in sera of Graves' patients. Thyroid stimulating anti-TSH-R antibodies (TSAb) are involved in the pathomechanism of thyrotoxicosis. The basic question is in this study whether TSAb exerts effects on metabolic activity of PMNs. Immunoglobulin G (IgGs) of 32 patients with thyrotoxicosis had significant inhibitory effect (p less than 0.001) on chemiluminescence of healthy PMNs compared to controls. An inverse correlation was observed between inhibitory effect of IgGs on function of PMNs and TT4 (r = -0.61) in contrast to anti-TSH-receptors antibodies (r = 0.09). TSAbs of eight hyperthyroid patients were measured by determination of cyclic AMP in suspension and slices of porcine thyroid gland. Function of human PMNs separated from healthy donors was determined by luminol-amplified chemiluminescence. Photon-emission of PMNs induced by adherence was significantly lower than that of controls. None of patients' IgGs contained anti-PMNs antibodies or other toxic compounds. It was found an inverse correlation between chemiluminescence of PMNs and capability of TSAb to increase intracellular cAMP in thyroid slices and the thyroid hormone levels of patients with thyrotoxicosis (p = 0.0005). In conclusion, TSH-R on PMNs did not belong to "mute" receptors and metabolic changes in PMNs induced by TSAb might have pathogenetic as well as methodological implications.