Abstract
Noting that corticosteroid doses required for protection in shock models exceeded those required to saturate glucocorticoid receptors in mammalian cells, we postulated a nonspecific physicochemical effect of steroids upon the cell membrane, and therefore tested three noncorticoid steroids for their effects on granulocyte function. All three (conjugated equine estrogen, a synthetic progestogen, and a synthetic androgen) behaved in manner analogous to corticoids at similar concentrations, inhibiting granulocyte aggregation, chemotaxis, and chemiluminescence, as well as binding to the granulocytes of the synthetic oligopepitide agonist f-Met-Leu-Phe. Estrogen was further shown to reduce granulocyte membrane fluidity, assessed by electron paramagnetic resonance. We propose that the unique effects of extremely high-dose corticosteroids are not mediated via the glucocorticoid receptor, but result rather from physicochemical effects of the drugs upon the membranes of effector cells.
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This work was supported in part by NIH grants HL-07062, HL-19725, and HL-30767, and was performed during Dr. Lamche's tenure as a visiting scientist at the University of Minnesota (from the Ludwig-Boltmann-Institut für experimentelle Traumatologie, Vienna). Portions of the work herein described were submitted by A.C.K. in partial fulfillment of the requirements for the degree, Bachelor of Science with Higher Honors, in the College of Biological Sciences of the University of Minnesota.
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Hammerschmidt, D.E., Knabe, A.C., Silberstein, P.T. et al. Inhibition of granulocyte function by steroids is not limited to corticoids. Inflammation 12, 277–284 (1988). https://doi.org/10.1007/BF00920079
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DOI: https://doi.org/10.1007/BF00920079