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Citations to this article

Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro.
K M Skubitz, … , D E Hammerschmidt, J T August
K M Skubitz, … , D E Hammerschmidt, J T August
Published July 1, 1981
Citation Information: J Clin Invest. 1981;68(1):13-20. https://doi.org/10.1172/JCI110228.
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Research Article

Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro.

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Abstract

Inhibition of complement-mediated granulocyte aggregation has recently been proposed as a mechanism of action of high-dose corticosteroids in shock states. Postulating that such inhibition might be effected through alteration of receptors function, we examined the effect of methylprednisolone (MP), hydrocortisone (HC), and dexamethasone (DEX) on the extent and kinetics of binding of the synthetic chemotaxin f-methionine-leucine-phenylalanine (FMLP) to its specific receptor on the granulocyte surface. Dose-dependent inhibition of binding was observed at corticosteroid concentrations paralleling plasma levels achieved with 30 mg/kg intravenous bolus therapy; the order of potency was MP greater than HC greater than DEX. Receptor number was unaffected by steroid exposure, but the steroids effected a decrease in association rate constant for the FMLP-receptor interaction (35% of N for 0.2 mg/ml MP), leading to decreased receptor-ligand affinity. Dissociation kinetics, as examined by cold-chase experiments, were unaltered by the corticosteroids. Furthermore, in addition to the inhibition of aggregation previously reported, aggregated granulocytes were found to disaggregate upon addition of corticosteroids; the order of potency was again MP greater than HC greater than DEX, with an MP concentration of approximately 2-3 mg/ml required to effect complete disaggregation. We conclude that corticosteroids can displace FMLP from the granulocyte surface by slowing association while allowing dissociation to proceed; altered kinetics of receptor-FMLP interaction may explain both the inhibition of granulocyte aggregation and granulocyte disaggregation. If these observations also hold for physiologic stimuli (such as C5adesarginine, which behaves similarly with respect to aggregation, inhibition, and disaggregation), such kinetic changes may be important in the clinical effects of very high-dose corticosteroids such as are administered in shock.

Authors

K M Skubitz, P R Craddock, D E Hammerschmidt, J T August

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Total citations by year

Year: 2024 2022 2019 2017 2015 2012 2011 2008 2006 2004 2003 2000 1998 1997 1996 1995 1993 1992 1991 1990 1989 1988 1987 1986 1985 1984 1983 1982 1981 Total
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Citations to this article in year 2011 (2)

Title and authors Publication Year
Annual Reports in Medicinal Chemistry
JJ Liu, TW Lee
Annual Reports in Medicinal Chemistry Volume 46 2011
Textbook of Critical Care
D Mesotten, GV Berghe
Textbook of Critical Care 2011

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