Adipocytokines leptin and adiponectin function as mast cell activity modulators

Abstract

Summary A growing body of data indicates that adipocytokines, including leptin and adiponectin, are critical components not only of metabolic regulation but also of the immune system, mainly by influencing the activity of cells participating in immunological and inflammatory processes. As mast cells (MCs) are the key players in the course of those mechanisms, this study aimed to evaluate the impact of leptin and adiponectin on some aspects of MC activity. We documented that in vivo differentiated mature tissue MCs from the rat peritoneal cavity express a receptor for leptin (OB‐R), as well as receptors for adiponectin (AdipoR1 and AdipoR2). We established that leptin, but not adiponectin, stimulates MCs to release of histamine as well as to generation of cysteinyl leukotrienes (cysLTs) and chemokine CCL2. We also found that both adipocytokines affect mRNA expression of various cytokines/chemokines. Leptin and adiponectin also activate MCs to produce reactive oxygen species. Moreover, we documented that leptin significantly augments the surface expression of receptors for cysLTs, i.e. CYSLTR1, CYSLTR2, and GPR17 on MCs, while adiponectin increases only GPR17 expression, and decreases CYSLTR2. Finally, we showed that both adipocytokines serve as potent chemoattractants for MCs. In intracellular signaling in MCs activated by leptin Janus‐activated kinase 2, phospholipase C, phosphatidylinositol 3‐kinase (PI3K), extracellular signal‐regulated kinase (ERK1/2), and p38 molecules play a part whereas the adiponectin‐induced activity of MCs is mediated through PI3K, p38, and ERK1/2 pathways. Our observations that leptin and adiponectin regulate MC activity might indicate that adipocytokines modulate the different processes in which MCs are involved.

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

“…Moreover, adiponectin exerts an antioxidant (oxidative and nitrative stress) activity that is AMPK-independent and that is largely mediated via PKA-dependent NF-κB inhibition ( 52 ). Importantly, adiponectin modulates the activity of several immune cells in the AT including macrophages ( 53 , 54 ), eosinophils ( 55 ), and mast cells ( 56 ). Indeed, profound mechanistic frameworks for this modulation are still lacking and require further investigation.…”

“…Indeed, these metabolic processes regulate MCs inflammatory cytokines and ROS production and IGE-mediated degranulation ( 203 , 204 , 230 ). A role for adipokines in the regulation of MC function has been recently revealed ( 56 ). Leptin and adiponectin were shown to exert opposite effects on MC polarization to promote a pro-inflammatory or an anti-inflammatory cytokine profile, respectively.…”

Adipokines and the control of mast cell functions: from obesity to inflammation?

“…In this issue, we report on a study that has identified new roles for leptin and adiponectin in controlling responses from mast cells . Mast cells from the rat peritoneal cavity were found to express the receptors for both leptin and adiponectin, and to respond to these adipokines by producing cytokines and reactive oxygen species.…”

The role of adipokines in the modulation of lymphoid lineage cell development and activity: An overview

“…The expression of adiponectin receptors has been also reported in immune cells, such as monocytes, 18 neutrophils 16 and mast cells. 19 Although both adiponectin receptors are found on the surface of natural killer (NK) cells, natural killer T (NKT) cells, B cells, CD4 + and CD8 + T lymphocytes, all these cells predominantly express AdipoR2. 20 Resistin is another prominent adipokine that together with RELMα, RELMβ and RELMγ belongs to the resistin-like molecule (RELM) family.…”