Chemokine-induced eosinophil recruitment. Evidence of a role for endogenous eotaxin in an in vivo allergy model in mouse skin.
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.
Teixeira
M M
MM
Applied Pharmacology, Imperial College School of Medicine at the National Heart and Lung Institute, London, SW3 6LY, United Kingdom. mauro.teixeira@ic.ac.uk
Wells
T N
TN
Lukacs
N W
NW
Proudfoot
A E
AE
Kunkel
S L
SL
Williams
T J
TJ
Hellewell
P G
PG
D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000494:pharmacology*; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D015936:Complement C5a / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007975:Leukotriene B4 / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D010972:Platelet Activating Factor / Q000494:pharmacology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D012867:Skin / Q000276:immunology*
C515457:Ccl11 protein, mouse; C515351:Ccr3 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D010972:Platelet Activating Factor; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D007975:Leukotriene B4; D015936:Complement C5a