Corticosteroids reversibly inhibit chemotactic peptide-receptor binding and
granulocyte response, yet allow desensitization and receptor down-
regulation
KM Skubitz and DE Hammerschmidt
Inhibition of complement-mediated granulocyte aggregation has recently been
proposed as a mechanism of action of high-dose corticosteroids in shock
states. Such inhibition may be effected through alteration of receptor
function. Methylprednisolone inhibits binding of the synthetic chemotaxin
f-methionine-leucine-phenylalanine (FMLP) to its surface receptor on
granulocytes in a dose-dependent manner by slowing the association rate of
the FMLP-receptor interaction without altering receptor number. Because the
half-life of high-dose methylprednisolone in vivo is short, we examined the
reversibility of its effects on granulocyte aggregation and receptor
function; both effects were readily reversed by washing. Furthermore,
methylprednisolone, at concentrations that profoundly inhibited the
granulocyte aggregation response to FMLP, allowed the occurrence of
FMLP-receptor down- regulation and granulocyte desensitization to further
stimulation by FMLP. We conclude that methylprednisolone at concentrations
that inhibit granulocyte aggregation can slow the rate of the FMLP-receptor
interaction while simultaneously allowing receptor down-regulation and
granulocyte desensitization to proceed. Transient blockade of granulocyte
function with concomitant desensitization and receptor down- regulation may
be important in the clinical effects of very high-dose corticosteroids such
as are administered in shock and could partially explain how drugs with
such short half-lives administered intermittently could exert a beneficial
effect in shock states. Similar observations may hold for other physiologic
stimuli.
Volume 68,
Issue 4,
pp. 830-836,
10/01/1986
Copyright © 1986 by The American Society of Hematology
