Calcitonin gene related peptide and N-procalcitonin modulate CD11b upregulation in lipopolysaccharide activated monocytes and neutrophils

Monneret, Guillaume; Arpin, Maud; Venet, Fabienne; Maghni, Karim; Debard, Anne-Lise; Pachot, Alexandre; Lepape, Alain; Bienvenu, Jacques

doi:10.1007/s00134-003-1759-2

Cited by 49 publications

(33 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies using activation-specific Abs show that Rap1 regulates both the avidity and affinity, but not the cell surface expression of integrin receptors (29,30,52). Elevated levels of cAMP, induced by treatment with rolipram and forskolin, have been shown previously to inhibit cell migration and Mac-1 expression (19,53). In our studies on human monocytes, activation of the Epac1-Rap1 pathway using 8-CPT-2Ј-O-Me-cAMP did not have any regulatory effects on ␤ 2 integrins.…”

Section: Discussionmentioning

confidence: 99%

The Cyclic AMP-Epac1-Rap1 Pathway Is Dissociated from Regulation of Effector Functions in Monocytes but Acquires Immunoregulatory Function in Mature Macrophages

Bryn

Mahic

Enserink

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

cAMP mediates its intracellular effects through activation of protein kinase A (PKA), nucleotide-gated ion channels, or exchange protein directly activated by cAMP (Epac). Although elevation of cAMP in lymphocytes leads to suppression of immune functions by a PKA-dependent mechanism, the effector mechanisms for cAMP regulation of immune functions in monocytes and macrophages are not fully understood. In this study, we demonstrate the presence of Epac1 in human peripheral blood monocytes and activation of Rap1 in response to cAMP. However, by using an Epac-specific cAMP analog (8-CPT-2′-O-Me-cAMP), we show that monocyte activation parameters such as synthesis and release of cytokines, stimulation of cell adhesion, chemotaxis, phagocytosis, and respiratory burst are not regulated by the Epac1-Rap1 pathway. In contrast, activation of PKA by a PKA-specific compound (6-Bnz-cAMP) or physiological cAMP-elevating stimuli like PGE2 inhibits monocyte immune functions. Furthermore, we show that the level of Epac1 increases 3-fold during differentiation of monocytes into macrophages, and in monocyte-derived macrophages cAMP inhibits FcR-mediated phagocytosis via both PKA and the Epac1-Rap1 pathway. However, LPS-induced TNF-α production is only inhibited through the PKA pathway in these cells. In conclusion, the Epac1-Rap1 pathway is present in both monocytes and macrophages, but only regulates specific immune effector functions in macrophages.

show abstract

Section: Discussionmentioning

confidence: 99%

The Cyclic AMP-Epac1-Rap1 Pathway Is Dissociated from Regulation of Effector Functions in Monocytes but Acquires Immunoregulatory Function in Mature Macrophages

Bryn

Mahic

Enserink

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Thus, it has been suggested that N-PCT is the fragment responsible for the biological effects of PCT. It has been shown that N-PCT modulates endotoxin-induced expression of CD11b, which is one of the major integrants involved in monocyte and neutrophil chemotaxis during a response to microbial infections [21]. Recently, we showed that N-PCT plays a critical role in the regulation of food intake and energy homeostasis [22].…”

Section: Introductionmentioning

confidence: 99%

Procalcitonin N-Terminal Peptide Causes Catabolic Effects via the Hypothalamus and Prostaglandin-Dependent Pathways

Tavares¹,

Miñano²

2008

Neuroendocrinology

View full text Add to dashboard Cite

Recent evidence suggests that the free amino-terminal fragment of procalcitonin (N-PCT) plays a role in the central control of feeding behavior and energy homeostasis. However, little is known about the mechanisms through which N-PCT works. Here we report that intracerebroventricular administration of N-PCT to free-feeding male rats induced a significant decrease of longer-term food intake and body weight gain. Conversely, N-PCT increased body temperature. We also show that intracerebroventricular administration of N-PCT induced a marked neuronal activation in key thermoregulatory and feeding areas of the hypothalamus. We further show that N-PCT increases the responsiveness of proopiomelanocortin anorexigenic neurons in the arcuate nucleus of the hypothalamus, and that stimulation of the de novo synthesis of prostaglandins is crucial for the central effects induced by N-PCT. Results support the role of N-PCT to the central control of feeding behavior and suggest that N-PCT, acting probably through the eicosanoid cyclooxygenase pathway, may act as a signaling molecule in the hypothalamus by regulating the activity of anorexigenic neurons in the hypothalamus.

show abstract

“…In line with this phenotypic modulation, CGRP-conditioned APC turned out to be poor stimulators of T cell proliferation in allogeneic and Ag-specific settings, an effect which was reverted by blocking IL-10 [115,116]. CGRP was also found to influence T cells and Mo migration and adhesion [118,119]. Moreover, IFN-γ release was diminished in the peripheral blood mononuclear cells (PBMC) of healthy donors activated with CGRP in vitro [116], whereas CGRP enhanced IL-13 release from the CLA+ memory T cells of some patients with atopic dermatitis [120].…”

Section: Neurogenic T Cell Immunomodulationmentioning

confidence: 98%

Modulation of CD4+ T Helper Cell Memory Responses in the Human Skin

Padovan

2017

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Immunological memory is defined as the capacity to mount faster and more effective immune responses against antigenic challenges that have been previously encountered by the host. CD4+ T helper (Th) cells play central roles in the establishment of immunological memory as they assist the functions of other leukocytes. Th cells express polarized cytokine profiles and distinct migratory and seeding capacities, but also retain a certain functional plasticity that allows them to modulate their proliferation, activity, and homing behaviour upon need. Thus, in healthy individuals, T cell immunomodulation fulfils the task of eliciting protective immune responses where they are needed. At times, however, Th plasticity can lead to collateral tissue damage and progression to autoimmune diseases or, conversely, incapacity to reject malignant tissues and clear chronic infections. Furthermore, common immune players and molecular pathways of diseases can lead to different outcomes in different individuals. A mechanistic understanding of those pathways is therefore crucial for developing precise and curative medical interventions. Here, I focus on the skin microenvironment and comprehensively describe some of the cellular and molecular determinants of CD4+ T cell memory responses in homeostatic and pathological conditions. In discussing the cellular network orchestrating cutaneous immunity, I comprehensively describe the bidirectional interaction of skin antigen-presenting cells and mononuclear phagocytes with Th17 lymphocytes, and examine how the outcome of this interaction is influenced by endogenous skin molecules, including sodium salts and neuropeptides.

show abstract

Calcitonin gene related peptide and N-procalcitonin modulate CD11b upregulation in lipopolysaccharide activated monocytes and neutrophils

Cited by 49 publications

References 52 publications

The Cyclic AMP-Epac1-Rap1 Pathway Is Dissociated from Regulation of Effector Functions in Monocytes but Acquires Immunoregulatory Function in Mature Macrophages

The Cyclic AMP-Epac1-Rap1 Pathway Is Dissociated from Regulation of Effector Functions in Monocytes but Acquires Immunoregulatory Function in Mature Macrophages

Procalcitonin N-Terminal Peptide Causes Catabolic Effects via the Hypothalamus and Prostaglandin-Dependent Pathways

Modulation of CD4+ T Helper Cell Memory Responses in the Human Skin

Contact Info

Product

Resources

About