AlphaB-crystallin and neutrophil activation
Abstract
As the most abundant immune cells in the human body, neutrophils are often the first cell type to come in contact with invading microbes. These granulocytes flock to the site of infection or injury during the acute phase of inflammation where they provide many anti-microbial effector mechanisms that are tightly regulated. These cells also contribute to the inflammatory environment by directing the responses of other immune cell populations through cytokine and chemokine secretion as well as communication via direct contact 1,2. If left unregulated during sterile injury or auto-inflammation, neutrophils can be harmful to the host and exacerbate the inflammatory response. This study aimed to elucidate mechanisms to regulate neutrophil response to stimulation.
AlphaB-crystallin (αBC) is a small heat shock protein that possesses protective functions including anti-inflammatory capabilities 3. This crystallin is the highest upregulated gene in active multiple sclerosis (MS) lesions 4 and studies have shown that αBC treatment of EAE animals (a model of MS) reduced clinical disease and suppressed T cell activation 5. I hypothesized that αBC plays a protective role in EAE by down-regulating the pro-inflammatory response of neutrophils.
Under stimulatory conditions in vitro, treatment with αBC induced neutrophils to secrete increased amounts of IL-10 and MMP-8 as well as returned the generation of reactive oxygen species toward unprimed levels. Further, when grown together with dendritic cells (DCs), prior αBC treatment of stimulated neutrophils reduced the production of IL-12p40 by DCs. Although neutrophils were upregulated and hypersensitive in response to the induction of the EAE model, treatment with αBC did not alter the phenotype of these cells during the disease course.
Neutrophils treated with αBC in vitro exibit an altered reponse to stimulation that ultimately reduces the stimulation of DCs. This mechanism does not appear to play a role during EAE since BC treatment did not translate to a suppression of neutrophils in the MS disease model. Since EAE is a T cell driven disease, it is possible that BC treatment of neutrophils may be more impactful in other diseases where these granulocytes play a prominent role such as rheumatoid arthritis or systemic lupus erythmatosis.
Description
Keywords
Biology, Neuroscience
Citation
Lichtenberger, T. M. (2017). AlphaB-crystallin and neutrophil activation (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/24776