Eosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected 111In-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, "eotaxin," exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1, 31% with human MIP-1 alpha, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2 pmol dose in the skin, but did not induce significant 111In-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-1 alpha, and MCP-1 were all inactive in inducing 111In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung.
Article|
March 01 1994
Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.
P J Jose,
P J Jose
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
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D A Griffiths-Johnson,
D A Griffiths-Johnson
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
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P D Collins,
P D Collins
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
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D T Walsh,
D T Walsh
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
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R Moqbel,
R Moqbel
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
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N F Totty,
N F Totty
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
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O Truong,
O Truong
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
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J J Hsuan,
J J Hsuan
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
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T J Williams
T J Williams
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
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P J Jose
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
D A Griffiths-Johnson
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
P D Collins
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
D T Walsh
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
R Moqbel
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
N F Totty
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
O Truong
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
J J Hsuan
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
T J Williams
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1994) 179 (3): 881–887.
Citation
P J Jose, D A Griffiths-Johnson, P D Collins, D T Walsh, R Moqbel, N F Totty, O Truong, J J Hsuan, T J Williams; Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.. J Exp Med 1 March 1994; 179 (3): 881–887. doi: https://doi.org/10.1084/jem.179.3.881
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