Complement C5a receptors in the pituitary gland: expression and function

Francis, Karen; Lewis, B. M.; Monk, Peter N.; Ham, Jack

doi:10.1677/joe-08-0110

Cited by 14 publications

(8 citation statements)

References 38 publications

(41 reference statements)

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“…Despite the controversy over the putative interaction between C5L2 and ASP, both proteins have been demonstrated to affect metabolism at the level of the central nervous system. Both C5L2 and C5aR are present in the anterior pituitary gland, and C5a was demonstrated to stimulate adrenocorticotropic hormone release; however, whether this effect is through C5aR or C5L2 is unclear (55). In addition, administration of ASP into the third ventricle promotes an anorexigenic state through modulation of neuropeptide Y and proopiomelanocortin expression (56).…”

Section: C5l2 Physiology and Pathophysiologymentioning

confidence: 99%

C5L2: a controversial receptor of complement anaphylatoxin, C5a

Li¹,

Coulthard²,

Wu³

et al. 2012

FASEB j.

180

158

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C5a is the paramount proinflammatory mediator of the complement cascade, and has been previously thought to act only through a single, G-protein-coupled, C5a receptor (C5aR; also termed CD88). In 2000, a second C5a receptor, C5L2 (previously known as GPR77), was discovered; yet, despite 12 yr of intensive research, its biological, or pathophysiological, function is both enigmatic and controversial. Unlike C5aR, this receptor does not couple to G proteins, and early studies promoted the hypothesis that C5L2 functions as a decoy receptor. However, recent data have provided other evidence for more complicated and conflicting interactions between C5L2 and other inflammatory mediators. C5L2 has been recently demonstrated to physically interact with both C5aR and β-arrestin to negatively regulate C5aR signaling toward an anti-inflammatory manner, and to reduce pathology, in several disease models in vivo. In direct contrast, other groups have demonstrated that C5L2 stimulation caused release of HMGB1 both in vitro and in vivo, and enhanced pathology in sepsis models, suggesting a clear proinflammatory signaling role. These astoundingly contradictory data challenge our precepts and complicate the foundational bases for the possible targeting of C5L2 as a therapeutic option in inflammatory disease. C5L2 may be the great masquerader in complement biology; its function dependent on the cell type, species, and disease context. Because of these unusual and unforeseen complexities, we present the current state of knowledge on C5L2 structure, expression and, most controversially, its putative functions.-Li, R., Coulthard, L.G., Wu, M. C. L., Taylor, S. M., Woodruff, T. M. C5L2: a controversial receptor of complement anaphylatoxin, C5a.

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Section: C5l2 Physiology and Pathophysiologymentioning

confidence: 99%

C5L2: a controversial receptor of complement anaphylatoxin, C5a

Li¹,

Coulthard²,

Wu³

et al. 2012

FASEB j.

180

158

View full text Add to dashboard Cite

show abstract

“…Complement proteins are constitutively produced and continuously circulate in the blood, and following contact with the surface of bacteria complement proteins can be rapidly activated, thus available to rapidly activate HPA responses. Complement products C3a and C5a have been shown to elevate ACTH (21,22) and activate paraventricular hypothalamic neurons (8) as well as act directly on the adrenal gland (21). Complement products can also trigger prostaglandin synthesis and release by Kupffer cells (45,47) adding to HPA activation.…”

Section: R1653 Time-dependent Mediators Of the Hpa Axis Following E mentioning

confidence: 99%

Time-dependent mediators of HPA axis activation following live Escherichia coli

Zimomra

Porterfield

Camp

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Zimomra ZR, Porterfield VM, Camp RM, Johnson JD. Time-dependent mediators of HPA axis activation following live Escherichia coli . Am J Physiol Regul Integr Comp Physiol 301: R1648-R1657, 2011. First published September 14, 2011 doi:10.1152/ajpregu.00301.2011.-The hypothalamus-pituitary-adrenal (HPA) axis is activated during an immune challenge to liberate energy and modulate immune responses via feedback and regulatory mechanisms. Inflammatory cytokines and prostaglandins are known contributors to HPA activation; however, most previous studies only looked at specific time points following LPS administration. Since whole bacteria have different immune stimulatory properties compared with LPS, the aim of the present studies was to determine whether different immune products contribute to HPA activation at different times following live Escherichia coli challenge. Sprague-Dawley rats were injected intraperitoneally with E. coli (2.5 ϫ 10 7 CFU) and a time course of circulating corticosterone, ACTH, inflammatory cytokines, and PGE2 was developed. Plasma corticosterone peaked 0.5 h after E. coli and steadily returned to baseline by 4 h. Plasma PGE2 correlated with the early rise in plasma corticosterone, whereas inflammatory cytokines were not detected until 2 h. Pretreatment with indomethacin, a nonselective cyclooxygenase inhibitor, completely blocked the early rise in plasma corticosterone, but not at 2 h, whereas pretreatment with IL-6 antibodies had no effect on the early rise in corticosterone but attenuated corticosterone at 2 h. Interestingly, indomethacin pretreatment did not completely block the early rise in corticosterone following a higher concentration of E. coli (2.5 ϫ 10 8 CFU). Further studies revealed that only animals receiving indomethacin prior to E. coli displayed elevated plasma and liver cytokines at early time points (0.5 and 1 h), suggesting prostaglandins suppress early inflammatory cytokine production. Overall, these data indicate prostaglandins largely mediate the early rise in plasma corticosterone, while inflammatory cytokines contribute to maintaining levels of corticosterone at later time points.corticosterone; prostaglandin; IL-6; indomethacin ACTIVATION OF THE hypothalamus-pituitary-adrenal (HPA) axis is one of the critical brain-mediated sickness responses that enhance survival of an organism during an immune challenge. The resulting elevation in circulating glucocorticoids, mainly cortisol in humans and corticosterone in mice and rats, liberate energy necessary to mount a fever and have numerous immunomodulatory effects that reduce the risk of septic shock and increase the chances of survival during infection (52, 53). For example, glucocorticoids suppress proinflammatory cytokines (2, 17, 34) and prostaglandin production (27, 38), stimulate anti-inflammatory cytokine production (16, 20), upregulate Fc receptors and major histocompatibility complex class II molecules on phagocytes (24), increase cell adhesion molecules on endothelial cells (57), enhance acute phase changes in t...

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“…Several biological processes in the body undergo circadian changes caused by i) the release of relevant hormones (e.g., the abovementioned melatonin and adrenal gland steroids), ii) the tonus in innervation of tissues by the sympathetic and parasympathetic autonomic nerve fibers, iii) the sleeping–waking rhythm, and iv) the effect of light on the organism [ 1 , 6 ]. Perturbation of the normal circadian rhythm may lead to organ dysfunction, accelerated atherosclerosis, and even neoplasm [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

A Circadian Rhythm in both Complement Cascade (ComC) Activation and Sphingosine-1-Phosphate (S1P) Levels in Human Peripheral Blood Supports a Role for the ComC–S1P Axis in Circadian Changes in the Number of Stem Cells Circulating in Peripheral Blood

Budkowska

Ostrycharz

Wojtowicz

et al. 2018

Stem Cell Rev and Rep

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The number of hematopoietic stem/progenitor cells (HSPCs) circulating in peripheral blood (PB) is regulated by a circadian rhythm, and more HSPCs circulate in PB in the morning hours than at night. Different mechanisms have been proposed that might regulate this process, including changes in tonus of β-adrenergic innervation of bone marrow (BM) tissue. Our group reported that in mice circadian changes in the number of HSPCs circulating in PB correlates with diurnal activation of the complement cascade (ComC) and that the mice deficient in C5 component of ComC (C5-KO mice) do not show circadian changes in the number of circulating HSPCs in PB. We also reported the existence of a gradient between PB and BM of a bioactive phosphosphingolipid, sphingosine-1-phosphate (S1P), which is a major PB chemottractant for BM-residing HSPCs. Based on these observations, we investigated activation of the ComC and the level of S1P in the PB of 66 healthy volunteers. We found that both ComC activation and the S1P level undergo changes in a circadian cycle. While the ComC becomes highly activated during deep sleep at 2 am, S1P becomes activated later, and its highest level is observed at 8 am, which precedes circadian egress of HSPCs from BM into PB. In sum, circadian activation of the ComC–S1P axis releases HSPCs from BM into PB.

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Complement C5a receptors in the pituitary gland: expression and function

Cited by 14 publications

References 38 publications

C5L2: a controversial receptor of complement anaphylatoxin, C5a

C5L2: a controversial receptor of complement anaphylatoxin, C5a

Time-dependent mediators of HPA axis activation following live Escherichia coli

A Circadian Rhythm in both Complement Cascade (ComC) Activation and Sphingosine-1-Phosphate (S1P) Levels in Human Peripheral Blood Supports a Role for the ComC–S1P Axis in Circadian Changes in the Number of Stem Cells Circulating in Peripheral Blood

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