The role of lipocortin-1 in the inhibitory action of dexamethasone on eosinophil trafficking in cutaneous inflammatory reactions in the mouse

Br J Pharmacol. 1998 Feb;123(3):538-44. doi: 10.1038/sj.bjp.0701625.

Abstract

1. The ability of glucocorticosteroids to inhibit tissue eosinophilia may be an important feature of their anti-inflammatory action in allergic diseases. Our previous work showed that an effect of dexamethasone on the release of eosinophils from the bone marrow could explain its inhibitory action on eosinophil accumulation in a mouse air-pouch model. Thus, it was unclear from that study whether dexamethasone could interfere with the process of eosinophil trafficking. In the present study, therefore, we used a newly developed mouse model to evaluate the effects of systemic treatment with dexamethasone on the recruitment of (111)In-labelled blood eosinophils to sites of cutaneous inflammation in the mouse and whether lipocortin-1 (LC-1) was involved. 2. The i.d. injection of ovalbumin (OVA) in sensitized mice induced a dose-dependent recruitment of (111)In-labelled blood eosinophils which peaked at 4 to 8 h after antigen challenge. Systemic treatment with dexamethasone (50 microg per mouse, 3 h after antigen) effectively inhibited (111)In-eosinophil recruitment in this reaction by 70 to 85%. Similarly, a 1 h pretreatment with dexamethasone significantly suppressed (111)In-eosinophil induced by platelet-activating factor (PAF), leukotriene B4(LTB4) and the chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) by 40 to 70%. 3. Two experimental approaches were used to evaluate the role of LC-1: treatment with LC-1 fragment Ac2-26 and use of an anti-LC-1 antiserum. LC-1 fragment Ac2-26 (100 microg per mouse) failed to affect (111)In-eosinophil recruitment. Moreover, pretreatment of animals with an anti-LC-1 antiserum failed to reverse the inhibitory effects of dexamethasone on (111)In-eosinophil recruitment induced by MIP-1alpha and by antigen in sensitized mice. 4. In contrast, the LC-1 fragment significantly inhibited glycogen-induced neutrophil recruitment into the peritoneal cavity of mice. Furthermore, the anti-LC-1 antiserum reversed the inhibitory effects of dexamethasone on the glycogen-induced neutrophil recruitment. 5. Thus, our results suggest that dexamethasone can inhibit the recruitment of eosinophils in mouse skin independent of an action on the bone marrow. However, by use of two different approaches, we showed that LC-1 does not play a role in mediating the inhibitory action of dexamethasone on eosinophil migration into cutaneous inflammatory reactions in the mouse. These data add further support to a LC-1-independent action of dexamethasone on eosinophils in vivo.

MeSH terms

  • Animals
  • Annexin A1 / immunology
  • Annexin A1 / physiology*
  • Cell Movement / drug effects
  • Chemotactic Factors / physiology
  • Dermatitis / blood*
  • Dexamethasone / pharmacology*
  • Disease Models, Animal
  • Eosinophils / cytology
  • Eosinophils / drug effects*
  • Immune Sera
  • Indium Radioisotopes
  • Mice
  • Mice, Inbred CBA
  • Neutrophils / cytology
  • Neutrophils / drug effects

Substances

  • Annexin A1
  • Chemotactic Factors
  • Immune Sera
  • Indium Radioisotopes
  • Dexamethasone