Search

Your search keyword '"Eamsamarng S"' showing total 4 results
Start Over Author "Eamsamarng S"
4 results on '"Eamsamarng S"'

2. Hypoxia-inducible factor 2α regulates key neutrophil functions in humans, mice, and zebrafish

Author

Thompson, A, Elks, P, Marriott, H, Eamsamarng, S, Higgins, K, Lewis, A, Williams, L, Parmar, S, Shaw, G, McGrath, E, Formenti, F, Van Eeden, F, Kinnula, V, Pugh, C, Sabroe, I, Dockrell, D, Chilvers, E, Robbins, P, Percy, M, Simon, M, Johnson, R, Renshaw, SA, Whyte, M, and Walmsley, SR

Subjects
Inflammation, Neutrophils, Green Fluorescent Proteins, Apoptosis, Immunohistochemistry, Cell Hypoxia, Mice, Inbred C57BL, Mice, Phagocytes, Granulocytes, and Myelopoiesis, Phenotype, Phagocytosis, Gene Expression Regulation, Basic Helix-Loop-Helix Transcription Factors, RNA, Animals, Humans, Muramidase, Zebrafish, Respiratory Burst
Abstract

Neutrophil lifespan and function are regulated by hypoxia via components of the hypoxia inducible factor (HIF)/von Hippel Lindau/hydroxylase pathway, including specific roles for HIF-1α and prolyl hydroxylase-3. HIF-2α has both distinct and overlapping biological roles with HIF-1α and has not previously been studied in the context of neutrophil biology. We investigated the role of HIF-2α in regulating key neutrophil functions. Human and murine peripheral blood neutrophils expressed HIF-2α, with expression up-regulated by acute and chronic inflammatory stimuli and in disease-associated inflammatory neutrophil. HIF2A gain-of-function mutations resulted in a reduction in neutrophil apoptosis both ex vivo, through the study of patient cells, and in vivo in a zebrafish tail injury model. In contrast, HIF-2α-deficient murine inflammatory neutrophils displayed increased sensitivity to nitrosative stress induced apoptosis ex vivo and increased neutrophil apoptosis in vivo, resulting in a reduction in neutrophilic inflammation and reduced tissue injury. Expression of HIF-2α was temporally dissociated from HIF-1α in vivo and predominated in the resolution phase of inflammation. These data support a critical and selective role for HIF-2α in persistence of neutrophilic inflammation and provide a platform to dissect the therapeutic utility of targeting HIF-2α in chronic inflammatory diseases.

Published
2014

3. T1 Hypoxia-Inducible Factor 2α Regulates Neutrophilic Inflammation in Humans, Mice and Zebrafish

Author

Thompson, AAR, primary, Elks, PM, additional, Marriott, HM, additional, Higgins, KR, additional, Parmar, S, additional, Shaw, G, additional, Eamsamarng, S, additional, McGrath, EE, additional, Formenti, F, additional, Eeden, FJ Van, additional, Kinnula, VL, additional, Pugh, CW, additional, Sabroe, I, additional, Dockrell, DH, additional, Chilvers, ER, additional, Robbins, PA, additional, Simon, MC, additional, Johnson, RS, additional, Renshaw, SA, additional, Whyte, MKB, additional, and Walmsley, SR, additional

Published
2012
Full Text
View/download PDF

4. Semaphorin 3F signaling actively retains neutrophils at sites of inflammation.

Author

Plant T, Eamsamarng S, Sanchez-Garcia MA, Reyes L, Renshaw SA, Coelho P, Mirchandani AS, Morgan JM, Ellett FE, Morrison T, Humphries D, Watts ER, Murphy F, Raffo-Iraolagoitia XL, Zhang A, Cash JL, Loynes C, Elks PM, Van Eeden F, Carlin LM, Furley AJ, Whyte MK, and Walmsley SR

Subjects
Animals, Humans, Inflammation immunology, Inflammation pathology, Mice, Neutrophils pathology, Up-Regulation immunology, Cell Movement immunology, Membrane Proteins immunology, Nerve Tissue Proteins immunology, Neutrophils immunology, Signal Transduction immunology, Zebrafish immunology, Zebrafish Proteins immunology
Abstract

Neutrophilic inflammation is central to disease pathogenesis, for example, in chronic obstructive pulmonary disease, yet the mechanisms that retain neutrophils within tissues remain poorly understood. With emerging evidence that axon guidance factors can regulate myeloid recruitment and that neutrophils can regulate expression of a class 3 semaphorin, SEMA3F, we investigated the role of SEMA3F in inflammatory cell retention within inflamed tissues. We observed that neutrophils upregulate SEMA3F in response to proinflammatory mediators and following neutrophil recruitment to the inflamed lung. In both zebrafish tail injury and murine acute lung injury models of neutrophilic inflammation, overexpression of SEMA3F delayed inflammation resolution with slower neutrophil migratory speeds and retention of neutrophils within the tissues. Conversely, constitutive loss of sema3f accelerated egress of neutrophils from the tail injury site in fish, whereas neutrophil-specific deletion of Sema3f in mice resulted in more rapid neutrophil transit through the airways, and significantly reduced time to resolution of the neutrophilic response. Study of filamentous-actin (F-actin) subsequently showed that SEMA3F-mediated retention is associated with F-actin disassembly. In conclusion, SEMA3F signaling actively regulates neutrophil retention within the injured tissues with consequences for neutrophil clearance and inflammation resolution.

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results