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Macrophage inflammatory protein-4a
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This protein of 73 amino acids has been found in the bronchoalveolar lavage of guinea pigs used as a model of allergic inflammation. The factor belongs to the platelet factor-4 family (see: PF4) of Chemokines. It 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. Eotaxin is 60 % identical with MCP-4 (Monocyte chemotactic protein-4). The gene symbol is SCYA11. The factor is being referred to also as Eotaxin-1 (following the identification of related factors Eotaxin-2, Eotaxin-3) and has been renamed CCL11. See also: SCY family of cytokines for a systematic nomenclature.
The protein sequence of human eotaxin is 66 % identical with human MCP-1, and 60 % identical with guinea pig eotaxin. For a structurally less related but functionally related factor see also: Eotaxin-2.
Eotaxin induces substantial accumulation of eosinophils at a 1-2 pmol dose in the skin without significantly affecting the accumulation of neutrophils. Eotaxin is a potent stimulator of both guinea pig and human eosinophils in vitro. The factor appears to share a binding site with RANTES on guinea pig eosinophils.
Recombinant human eotaxin induces a calcium flux response in normal human eosinophils, but not in neutrophils or monocytes. The response cannot be desensitized by pretreatment of eosinophils with other CC-Chemokines, suggesting a unique receptor. In basophils Eotaxin induces higher levels of chemotactic response than RANTES but it has only a marginal effect on either histamine release or leukotriene C 4 generation.
The receptor is a G-protein-coupled receptor selectively expressed in human eosinophils (see also: CCR3).
Ponath et al (1996) have described a receptor on eosinophils, designated CKR3, that is distinct from the known receptors for Chemokines designated CCR1 and CCR2. CKR3 is not expressed on other types of leukocytes. The CKR3 receptor also binds RANTES and MCP-3 with high affinity, but not other CC-Chemokines or or CXC-Chemokines. Murine B-cell lymphoma cells engineered to express CKR3 migrate in response to eotaxin, RANTES, and MCP-3, but not to any other chemokines. A viroceptor encoded by equine herpesvirus 2 (see: EHV-2 E1 orf) has been shown to bind Eotaxin.
Like some chemokines, and unlike other chemokines, that do, Eotaxin does not possess suppressive activity against immature subsets of myeloid progenitors (see also: hematopoiesis) stimulated to proliferate by multiple growth factors (Broxmeyer et al (1999).
Bartels et al (1996) have demonstrated the presence of eotaxin sequence variants and of low constitutive eotaxin mRNA expression in human dermal fibroblasts, which is upregulated by IL1-alpha or TNF-alpha within 6 hrs and modulated by IFN-gamma. Induction by IL1-alpha is transient while long-term stimulation with TNF-alpha results in a further increase of eotaxin mRNA.
This factor is known mainly because of its chemotactic activity. For an unrelated function as an antimicrobial peptide in innate immunity see: CCL11. For other proteins/peptides with functions in innate immunity and/or antimicrobial activities see also: Innate immunity defense peptides Dictionary.
Copyright © 2012 by H IBELGAUFTS. All rights reserved.
ENTRY LAST MODIFIED: January 2002
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