Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.

Abstract

SllmmsLryEosinophil 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-loe, 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-lcr, and MCP-1 were all inactive in inducing ~11In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with P.ANTES 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.

Comparative efficacy and safety of aliskiren and irbesartan in patients with hypertension and metabolic syndrome

“…30 Measurements of a large panel of biomarkers of inflammation and cardiovascular risk showed few statistically significant differences from baseline levels. Only the inflammatory mediator eotaxin 31 showed a statistically significant between-treatment difference, but the clinical significance of this finding is uncertain. Both aliskiren and irbesartan reduced levels of F 2 isoprostane (a marker of oxidative stress) and endothelin-1 (a potent vasoconstrictor).…”

Inflammaging impairs peripheral nerve maintenance and regeneration

“…MCP1 as a potent macrophage attracting factor is known to be expressed by denervated Schwann cells (Deshmane, Kremlev, Amini, & Sawaya, 2009; Tofaris, Patterson, Jessen, & Mirsky, 2002). CCL11, also known as eotaxin‐1, has been identified as chemoattractant for eosinophile immune cells (Jose et al, 1994) and is stated to be secreted by M1 and M2 macrophages (Arango Duque & Descoteaux, 2014; Herranz, Traves, Luque, & Hortelano, 2012). Both cytokines have been found locally expressed in sciatic nerves within two days after injury (van Rossum, Hilbert, Strassenburg, Hanisch, & Bruck, 2008).…”

Using guinea pigs in studies relevant to asthma and COPD

“…In both species, a component of the response to these constricting agonists is reflex in nature [35]. Inflammatory autacoids, chemokines and cytokines including LTD 4 , LTB 4 , TNFα, IL-5, IL-8, IL-13, PAF and eotaxin induce inflammation and cellular infiltration into the airway wall and the airspaces of guinea pigs as they are likely to do or have been shown to produce in human subjects [11][12][13]87,147,. Mucus secretion and mucus production can be induced in both species by muscarinic receptor agonists, the cysteinyl-leukotrienes, elastase, TNFα, IL-13 and PAF [34,38,155,172,[175][176][177][178][179][180][181][182][183].…”

“…Many fundamental processes, mediators and regulators of airways disease pathogenesis were discovered or demonstrated first in guinea pigs, including the Schultz-Dale (immediate type hypersensitivity) reaction, the actions of histamine, the cysteinyl-leukotrienes and their two receptors, beta adrenoceptor subtypes, thromboxane, vascular endothelial growth factor (VEGF), eotaxin, alveolar macrophage derived neutrophil chemotactic factor(s) (leukotriene B 4 and/or IL-8) and the roles of cAMP and inositol triphosphate in signal transduction [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Receptor pharmacology in guinea pigs more closely matches that of human receptor pharmacology than most other commonly used species [1,20,21] (Table 1, Figs.…”