The Effect of Glucocorticoids on the Expression of L-Selectin on Polymorphonuclear Leukocyte

Abstract

When active bone marrow release is induced by inflammatory stimuli, it is associated with an increase in L-selectin expression on circulating polymorphonuclear leukocyte (PMN). This contrasts sharply with glucocorticoid-induced granulocytosis that is associated with decreased L-selectin expression on PMN. The present study was designed to determine if the reduced L-selectin expression observed after glucocorticoid treatment is the result of suppression of L-selectin synthesis in the bone marrow. New Zealand white rabbits treated with dexamethasone (2.0 mg/kg, a single dose intravenously) were shown to have decreased L-selectin expression on circulating PMN 12 to 24 hours after treatment (P < .01) with a return to baseline levels by 48 hours. When dexamethasone was administered 48 hours after the bone marrow PMN were pulse labeled with the thymidine analogue, 5′-bromo-2′-deoxyuridine (BrdU), L-selectin expression on BrdU-labeled PMN released from the bone marrow was decreased (P< .01). Dexamethasone decreased L-selectin expression on segmented PMN in the bone marrow (P < .05) but not on PMN already in the circulation. We conclude that glucocorticoids decrease L-selectin expression on circulating PMN by downregulating L-selectin expression in the maturation pool of bone marrow and speculate that this is an important glucocorticoid effect that influences the recruitment of PMN into inflammatory sites.

Endogenous glucocorticoids control neutrophil mobilization from bone marrow to blood and tissues in non‐inflammatory conditions

“…It is likely that high concentrations of endogenous glucocorticoids control the number of leukocytes in circulation in stress conditions as leukocytosis is one of the characteristics of hormone therapy (Harris et al , 1995; Liles et al , 1997; Nakagawa et al , 1998; Weber et al , 2001, 2004). The mechanism involved in these conditions seems to be related to a change in the longevity of the cell in the circulation induced by altering apoptosis (Chang et al , 2004; Madsen‐Bouterse et al , 2006) or by impairing the synthesis and expression of L‐selectin (Nakagawa et al , 1999; Weber et al , 2001, 2004). Our data suggest that endogenous glucocorticoids act as a selective modulator of the delivery of granulocyte cells from the bone marrow, as ADX (Cavalcanti et al , 2006) and RU 38486‐treated rats presented an increased rate of neutrophil maturation in the bone marrow with consequent neutrophilia, but with no effects on the lymphocyte/mononuclear cell lineages.…”

“…Endogenous glucocorticoids modulate several physiological responses, such as glucose metabolism, cardiovascular activity and immune reactions (Wilckens and De Rijk, 1997; Marik and Zaloga, 2002). Indeed, regulation of leukocyte recruitment (Flower et al , 1986; Moraes et al , 1987; Abe et al , 1995; Rovai et al , 1998; Leech et al , 2000), increase in vascular permeability, secretion of cytokines, expression of adhesion molecules, phagocytic and microbicidal activities (Filep et al , 1997; Fassbender et al , 1999; Nakagawa et al , 1999; Torsteinsdottir et al , 1999; Weber et al , 2001, 2004), which occur in the course of an inflammatory or stress injury, are modulated by an increase in the concentration of endogenous glucocorticoids in the plasma. In addition to the effects exerted by endogenous hormones, synthetic hormones are important therapeutic tools for the treatment of inflammatory diseases and as immunosuppressor agents (Rhen and Cidlowski, 2005; Song et al , 2005).…”

Interleukin-6 induces demargination of intravascular neutrophils and shortens their transit in marrow

“…Interleukin-6 induces an acute phase response that includes stimulation of the hypothalamic-pituitary-adrenal axis, resulting in a threefold increase in cortisol levels, which peak 2 h after the administration of IL-6 (27). We previously showed that steroids cause a rapid demargination of PMNs (17) and that this demargination is accompanied by a decrease in L-selectin levels on circulating PMNs (16). The reduction in L-selectin on PMN observed in these studies could be a direct effect of IL-6 treatment or a secondary effect related to an increase in circulating corticosteroids, and we postulate that it may play an important role in the demargination induced by IL-6.…”

Neuroendocrine Regulation of Immunity

“…Repression by glucocorticoids does not affect NFκB translocation or binding to DNA, which suggests interference in transcriptional activation of NFκB (70). L-selectin is involved in the attachment of blood leukocytes during inflammation, and its expression is decreased by glucocorticoid treatment in bone marrow cells and polymorphonuclear cells (104).…”