Chemokine-induced eosinophil recruitment. Evidence of a role for endogenous eotaxin in an in vivo allergy model in mouse skin

J Clin Invest. 1997 Oct 1;100(7):1657-66. doi: 10.1172/JCI119690.

Abstract

Selective eosinophil recruitment into tissues is a characteristic feature of allergic diseases. Chemokines are effective leukocyte chemoattractants and may play an important role in mediating eosinophil recruitment in various allergic conditions in man. Here, we describe a novel mouse model of eosinophil recruitment in which we have compared the in vivo chemoattractant activity of different C-C chemokines. Furthermore, we describe the use of antibodies to chemokines and receptor blockade to address the endogenous mechanisms involved in eosinophil recruitment in a late-phase allergic reaction in mouse skin. Intradermal injection of mEotaxin and mMIP-1alpha, but not mMCP-1, mRANTES, mMCP-5, or mMIP-1beta, induced significant 111In-eosinophil recruitment in mouse skin. Significant 111In-eosinophil recruitment was also observed in an active cutaneous anaphylactic reaction. Pretreatment of skin sites with antieotaxin antiserum, but not an antiMIP-1alpha antibody, suppressed 111In-eosinophil recruitment in this delayed-onset allergic reaction. Similarly, desensitization of the eosinophil eotaxin receptor CCR3 with mEotaxin, or blockade of the receptor with metRANTES, significantly inhibited 111In-eosinophil recruitment in the allergic reaction. These results demonstrate an important role for endogenous eotaxin in mediating the 111In-eosinophil recruitment in allergic inflammation, and suggest that blockade of the CCR3 receptor is a valid strategy to inhibit eosinophil migration in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anaphylaxis / immunology
  • Animals
  • Chemokine CCL11
  • Chemokines, CC / pharmacology*
  • Chemotactic Factors, Eosinophil / metabolism
  • Chemotaxis, Leukocyte*
  • Complement C5a / pharmacology
  • Cytokines / metabolism
  • Eosinophils / immunology*
  • Female
  • Hypersensitivity / immunology*
  • Hypersensitivity, Delayed / immunology
  • Leukotriene B4 / pharmacology
  • Mice
  • Mice, Inbred CBA
  • Platelet Activating Factor / pharmacology
  • Receptors, CCR3
  • Receptors, Chemokine / metabolism
  • Skin / immunology*

Substances

  • Ccl11 protein, mouse
  • Ccr3 protein, mouse
  • Chemokine CCL11
  • Chemokines, CC
  • Chemotactic Factors, Eosinophil
  • Cytokines
  • Platelet Activating Factor
  • Receptors, CCR3
  • Receptors, Chemokine
  • Leukotriene B4
  • Complement C5a