Eotaxin Triggers Eosmophil-Selective Chemotaxis and Calcium Flux via a Distinct Receptor and Induces Pulmonary Eosinophilia in the Presence of Interleukin 5 in Mice
Marc E. Rothenberg, Robert Ownbey, Paul D. Mehlhop, Paul M. Loiselle, Matthijs van de Rijn, Joseph V. Bonventre, Hans C. Oettgen, Philip Leder, Andrew D. Luster
Abstract
Understanding the processes that control selective eosinophilia is of fundamental importance in a variety of human diseases (e.g., allergies, parasitic infections, malignancy). Interleukin 5, an eosinophil-specific growth and activating factor, and eotaxin appear to collaborate in this process. Eotaxin is a recently described chemotactic factor that belongs to the C-C (or beta) chemokine family and has been implicated in animal and human eosinophilic inflammatory states. We have recently reported the molecular characterization of murine eotaxin and now report the biological properties of purified recombinant murine eotaxin in vitro and in vivo in the presence or absence of interleukin 5 (IL-5) in mice.
Murine eotaxin was expressed in bacteria and purified by affinity chromatography and HPLC. Activity was tested in vitro by examining chemotactic and calcium flux responses of purified murine leukocytes. Additionally, desensitization of calcium flux responses to other chemokines, eosinophil survival assays, and basophil histamine release were examined. Finally, eotaxin was delivered to wild-type or IL-5 transgenic mice and the host response was examined.
Eotaxin had activity only when the recombinant molecule had the native mature amino terminus and contained the first 25 amino acids of the mature protein. It was active in vitro at an effective concentration between 10 and 100 ng/ml in both chemotaxis and calcium flux assays toward eosinophils, but not macrophages or neutrophils. Furthermore, intranasal or subcutaneous application of eotaxin selectively recruited large numbers of eosinophils into the mouse lung and skin, respectively, only in the presence of interleukin 5. Macrophage inflammatory protein-1 alpha, a related C-C chemokine active on eosinophils, and eotaxin were not able to cross-desensitize. Eotaxin had no affect on the in vitro survival of eosinophils and did not induce basophil histamine release.
Mouse eotaxin is an eosinophil specific chemoattractant that has a markedly enhanced effect in vivo in the presence of another eosinophil selective cytokine IL-5, and utilizes a signal transduction receptor pathway that is distinct from that utilized by macrophage inflammatory protein-1 alpha. This data suggests that the development of tissue eosinophilia in vivo involves a two-step mechanism elicited by interleukin 5 and eotaxin.
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 April 2015.
All research outputs
#8,537,346
of 25,382,440 outputs
Outputs from Molecular Medicine
#419
of 1,206 outputs
Outputs of similar age
#8,410
of 26,604 outputs
Outputs of similar age from Molecular Medicine
#3
of 5 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,206 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.6. This one is in the 41st percentile – i.e., 41% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 26,604 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 8th percentile – i.e., 8% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 5 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.
