Immune challenges decrease biliverdin concentration in the spleen of northern Bobwhite quail, Colinus virginianus

Abstract

Most antioxidants have multiple functions; in addition to minimizing oxidative damage, many antioxidants have immune-modulating properties. For example, biliverdin is produced in the liver and spleen from the breakdown of heme, and has putative immune-suppressing and antioxidant properties. However, the majority of these properties have been investigated in vitro or in mammalian models, in which biliverdin reductase converts virtually all biliverdin to bilirubin. Thus, biliverdin's physiological roles remain largely untested. Here, we investigated whether biliverdin has immunomodulating roles by injecting Northern Bobwhite quail (Colinus virginianus) with either a vehicle control, lysed and rinsed pig red blood cells (pRBC) that contain erythrocyte antigens but no heme, or intact pRBC that contain both erythrocyte antigens and hemoglobin, thus increasing the amount of heme that can be converted to biliverdin. We then quantified hemagglutination and hemolysis ability, and biliverdin concentration in the liver and spleen, on 3, 6, and 9 days post-injection. We found that hemagglutination was greater in individuals that received intact pRBC, but not in those injected with heme-removed pRBC, demonstrating that biliverdin does not suppress immune function at this dosage. Biliverdin levels of liver and spleen were correlated within individuals, suggesting organism-level variation in biliverdin production. Lastly, individuals injected with intact pRBC had a reduced biliverdin concentration in the spleen, suggesting that immune challenges may reduce biliverdin production or accumulation. This initial investigation demonstrated that biliverdin may have more nuanced physiological roles than previously reported, supporting the value of further investigations into the physiology of biliverdin.

Production of biliverdin by biotransformation of exogenous heme using recombinant Pichia pastoris cells

“…As an intermediate metabolite in heme metabolism, biliverdin has long been regarded as a mere waste product excreted in bile. However, recent studies have revealed that it has many therapeutic effects on the human body, including antioxidant and anti-inflammatory properties (Vasavda et al 2019 ; Shiels et al 2020 ; McDonagh 2010 ; Gonzalez-Sanchez et al 2016 ), suppression of the immune response (Baylor and Butler 2019 ; Homsher et al 2018 ), stabilization of vascular endothelial cells (Nakao et al 2005 ; Li et al 2021 ), and regulation of cell apoptosis (Zheng et al 2014 ; Moraes et al 2012 ). Biliverdin is expected to be a potential therapeutic drug for many diseases.…”

Experimentally impaired female condition does not affect biliverdin‐based egg colour

“…The source of biliverdin deposited in the eggshell by female birds is thought to be in the uterus (Hargitai et al 2017). However, the exact connection between the biliverdin destined to colour the eggshell and that derived from the systemic degradation of the erythrocytes has yet to be described (Homsher et al 2018). Several studies on different species have found a link between eggshell colouration and female body condition, some of which provide support for a condition‐dependence of biliverdin‐based egg colour by following an observational approach (Moreno et al 2005, 2013, Siefferman et al 2006, Hanley et al 2008).…”

Immune challenge-induced oxidative damage may be mitigated by biliverdin

“…Thus, if immune challenges affect circulating triglyceride levels, then biliverdin concentration may also change proportionally via an unidentified mechanism. Given the nascent stage of research into the physiological roles of biliverdin in non-mammalian systems (Homsher et al, 2018;Butler and Ligon, 2015), documenting such potential associations may allow for development and refinement of more specific hypotheses.…”