ARDC Research Link Australia

ORCID Profile
Orcid icon. 0000-0001-5958-3739

Current Organisations
University of Calgary , McGill University , Lady Davis Institute for Medical Research , University of California Riverside

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Publications

Publication

Lipopolysaccharide-Stimulated or Granulocyte-Macrophage Colony-Stimulating Factor-Stimulated Monocytes Rapidly Express Biologically Active IL-15 on Their Cell Surface Independent of New Protein Synthe

Publisher: The American Association of Immunologists

Date: 11-2001

DOI: 10.4049/JIMMUNOL.167.9.5011

Abstract: Although IL-15 shares many of the biological activities of IL-2, IL-2 expression is primarily under transcriptional regulation, while the mechanisms involved in the regulation of IL-15 are complex and not completely understood. In the current study, we found that CD14+ monocytes constitutively exhibit both IL-15 mRNA and protein. IL-15 protein was found stored intracellularly and stimulation of CD14+ monocytes with either LPS or GM-CSF resulted in mobilization of IL-15 stores to the plasma membrane. This rapidly induced surface expression was the result of a translocation of preformed stores, confirming that posttranslational regulatory stages limit IL-15, because it was not accompanied by an increase in IL-15 mRNA and occurred independent of de novo protein synthesis. After fixation, activated monocytes, but not resting monocytes, were found to support T cell proliferation, and this effect was abrogated by the addition of an IL-15-neutralizing Ab. The presence of preformed IL-15 stores and the ability of stimulated monocytes to mobilize these stores to their surface in an active form is a novel mechanism of regulation for IL-15.

Publication

Stratospheric ozone depletion and tropospheric ozone increases drive Southern Ocean interior warming

Publisher: Springer Science and Business Media LLC

Date: 31-03-2022

DOI: 10.1038/S41558-022-01320-W

Publication

Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury

Publisher: American Association for the Advancement of Science (AAAS)

Date: 04-02-2022

DOI: 10.1126/SCIADV.ABM0142

Abstract: The mechanisms that drive leukocyte recruitment to the kidney are incompletely understood. Dipeptidase-1 (DPEP1) is a major neutrophil adhesion receptor highly expressed on proximal tubular cells and peritubular capillaries of the kidney. Renal ischemia reperfusion injury (IRI) induces robust neutrophil and monocyte recruitment and causes acute kidney injury (AKI). Renal inflammation and the AKI phenotype were attenuated in Dpep1 −/− mice or mice pretreated with DPEP1 antagonists, including the LSALT peptide, a nonenzymatic DPEP1 inhibitor. DPEP1 deficiency or inhibition primarily blocked neutrophil adhesion to peritubular capillaries and reduced inflammatory monocyte recruitment to the kidney after IRI. CD44 but not ICAM-1 blockade also decreased neutrophil recruitment to the kidney during IRI and was additive to DPEP1 effects. DPEP1, CD44, and ICAM-1 all contributed to the recruitment of monocyte/macrophages to the kidney following IRI. These results identify DPEP1 as a major leukocyte adhesion receptor in the kidney and potential therapeutic target for AKI.

Publication

The Pacific Decadal Oscillation modulated marine heatwaves in the Northeast Pacific during past decades

Publisher: Springer Science and Business Media LLC

Date: 19-06-2023

DOI: 10.1038/S43247-023-00863-W

Abstract: The Pacific Decadal Oscillation has been suggested to play an important role in driving marine heatwaves in the Northeast Pacific during recent decades. Here we combine observations and climate model simulations to show that marine heatwaves became longer, stronger and more frequent off the Northeast Pacific coast under a positive Pacific Decadal Oscillation scenario, unlike what is found during a negative Pacific Decadal Oscillation scenario. This primarily results from the different mean-state sea surface temperatures between the two Pacific Decadal Oscillation phases. Compared to the cool (negative) phase of the Pacific Decadal Oscillation, warmer coastal sea surface temperatures occur during the positive Pacific Decadal Oscillation phase due to reduced coastal cold upwelling and increased net downward surface heat flux. Model results show that, relative to the background anthropogenic global warming, the positive Pacific Decadal Oscillation in the period 2013–2022 prolongs marine heatwaves duration by up to 43% and acts to increase marine heatwaves annual frequency by up to 32% off the Northeast Pacific coast.

Publication

Monocyte Surface-Bound IL-15 Can Function as an Activating Receptor and Participate in Reverse Signaling

Publisher: The American Association of Immunologists

Date: 04-2004

DOI: 10.4049/JIMMUNOL.172.7.4225

Abstract: IL-15 is a short chain, four-α helix cytokine that shares some biological function with IL-2. One striking difference between IL-2 and IL-15 is the ability of monocytes to express IL-15 on their cell surface after activation. In the current study we have investigated the ability of human monocyte cell surface IL-15 to participate in reverse signaling. Cross-linking anti-IL-15 Abs were used as a surrogate ligand for surface IL-15 engagement. Ligation of cell surface-expressed IL-15 induced monocyte adhesion that required the activity of small m.w. GTPases. Reverse signals through surface IL-15 activated the Rho-GTPase Rac3. In addition, engagement of cell surface IL-15 was found to activate a number of signaling pathways, including both extracellular signal-regulated kinase 1/2 and p38, and resulted in the secretion of IL-8. IL-8 production required mitogen-activated protein kinase activity. Thus, the current study has established that cell surface IL-15 is more than just a ligand it can function as a receptor and participate in reverse signaling that results in cellular adhesion and production of inflammatory cytokines.