Methylprednisolone inhibits three classes of neutrophil receptors in human blood in vitro.
An analysis of receptor modulation on the neutrophil cell surface is essential for gaining insight into the activation and function of neutrophils in host defense. Moreover, agents that regulate the expression of surface receptors may have profound implications in the management of host response to infection. With this study, we extend previous observations in isolated cells of the putative ability of methylprednisolone sodium succinate (MPSS) to inhibit ligand binding to the formyl peptide receptor. Because neutrophils are exquisitely sensitive to isolation conditions, we have analyzed the regulation of receptor expression using flow cytometry in whole blood. This technique allows discrimination of neutrophils from other formed elements without isolation. Quiescent cells in blood exhibit low levels of formyl peptide receptor, CD11b/CD18, and CD14. We show that MPSS blocks upregulation of each of these receptors in response to three different stimuli (formyl peptide, lipopolysaccharide, and granulocyte macrophage colony-stimulating factor). The inhibition is reversible with an ED50 of approximately 0.4 mg/ml. From these observations, we conclude that the action of MPSS on neutrophils blocks a common response of receptors. Since these receptors probably function in part through independent signaling pathways, MPSS may function at a common site related to vesicular trafficking. Further investigation is needed to determine the specific means by which corticosteroids interfere with neutrophil upregulation mechanisms.
Brandt
M M
MM
Department of Surgery, University of New Mexico School of Medicine, Albuquerque 87131.
Lynam
E
E
Sklar
L A
LA
D001769:Blood / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008775:Methylprednisolone / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000187:drug effects*
D011956:Receptors, Cell Surface; D008775:Methylprednisolone