J Bacteriol Virol.  2016 Mar;46(1):47-51. 10.4167/jbv.2016.46.1.47.

Mast Cells and Lipid Mediators

• Cho KA

• KMID: 2168743
• DOI: http://doi.org/10.4167/jbv.2016.46.1.47

Abstract

Human mast cells are potent effector cells in host defense mechanisms of innate and acquired immunity, including inflammatory diseases such as asthma and atherosclerosis. Mast cells originate from pluripotent hematopoietic progenitors in the bone marrow. Activation of mast cells by different stimuli triggers the release of a large range of mediators, including de novo synthesized eicosanoids which are highly biologically active lipid mediators. For the generation of lipid mediators, cytoplasmic lipid droplets have been shown to function as a major intracellular pool of arachidonic acid, the precursor for eicosanoids biosynthesis. The article summarizes current knowledge on mast cell biosynthesis of lipid mediator and the role in inflammation.

Keyword

Mast cell; Lipid droplet; Eicosanoids; Inflammation

MeSH Terms

Adaptive Immunity
Arachidonic Acid
Asthma
Atherosclerosis
Bone Marrow
Cytoplasm
Defense Mechanisms
Eicosanoids
Humans
Inflammation
Mast Cells*
Arachidonic Acid
Eicosanoids

Reference

1). Weller CL, Collington SJ, Williams T, Lamb JR. Mast cells in health and disease. Clin Sci (Lond). 2011; 120:473–84.

2). Burton OT, Oettgen HC. Beyond immediate hyper-sensitivity: evolving roles for IgE antibodies in immune homeostasis and allergic diseases. Immunol Rev. 2011; 242:128–43.

3). Krystel-Whittemore M, Dileepan KN, Wood JG. Mast Cell: A Multi-Functional Master Cell. Front Immunol. 2015; 6:620.

4). Maaninka K, Lappalainen J, Kovanen PT. Human mast cells arise from a common circulating progenitor. J Allergy Clin Immunol. 2013; 132:463–9. e463.

5). Galli SJ, Tsai M, Wershil BK, Tam SY, Costa JJ. Regulation of mouse and human mast cell development, survival and function by stem cell factor, the ligand for the c-kit receptor. Int Arch Allergy Immunol. 1995; 107:51–3.

6). Juremalm M, Nilsson G. Chemokine receptor expression by mast cells. Chem Immunol Allergy. 2005; 87:130–44.

7). Dahlin JS, Hallgren J. Mast cell progenitors: origin, development and migration to tissues. Mol Immunol. 2015; 63:9–17.

8). Lennartsson J, Ronnstrand L. Stem cell factor receptor/c-Kit: from basic science to clinical implications. Physiol Rev. 2012; 92:1619–49.

9). Harvima IT, Nilsson G. Mast cells as regulators of skin inflammation and immunity. Acta Derm Venereol. 2011; 91:644–50.

10). Wernersson S, Pejler G. Mast cell secretory granules: armed for battle. Nat Rev Immunol. 2014; 14:478–94.

11). Gandotra S, Le Dour C, Bottomley W, Cervera P, Giral P, Reznik Y, et al. Perilipin deficiency and autosomal dominant partial lipodystrophy. N Engl J Med. 2011; 364:740–8.

12). D'Avila H, Maya-Monteiro CM, Bozza PT. Lipid bodies in innate immune response to bacterial and parasite infections. Int Immunopharmacol. 2008; 8:1308–15.

13). Zehmer JK, Huang Y, Peng G, Pu J, Anderson RG, Liu P. A role for lipid droplets in inter-membrane lipid traffic. Proteomics. 2009; 9:914–21.

14). Bozza PT, Bakker-Abreu I, Navarro-Xavier RA, Bandeira -Melo C. Lipid body function in eicosanoid synthesis: an update. Prostaglandins Leukot Essent Fatty Acids. 2011; 85:205–13.

15). Kulinski JM, Munoz-Cano R, Olivera A. Sphingosine-1-phosphate and other lipid mediators generated by mast cells as critical players in allergy and mast cell function. Eur J Pharmacol. 2015. DOI: doi: 10.1016/j.ejphar.2015.02.058.

16). Robenek H, Hofnagel O, Buers I, Robenek MJ, Troyer D, Severs NJ. Adipophilin-enriched domains in the ER membrane are sites of lipid droplet biogenesis. J Cell Sci. 2006; 119:4215–24.

17). Dichlberger A, Schlager S, Lappalainen J, Kakela R, Hattula K, Butcher SJ, et al. Lipid body formation during maturation of human mast cells. J Lipid Res. 2011; 52:2198–208.

18). Dichlberger A, Schlager S, Maaninka K, Schneider WJ, Kovanen PT. Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells. J Lipid Res. 2014; 55:2471–8.

19). Zechner R, Zimmermann R, Eichmann TO, Kohlwein SD, Haemmerle G, Lass A, et al. FAT SIGNALS– lipases and lipolysis in lipid metabolism and signaling. Cell Metab. 2012; 15:279–91.

20). Nantel F, Fong C, Lamontagne S, Wright DH, Giaid A, Desrosiers M, et al. Expression of prostaglandin D synthase and the prostaglandin D2 receptors DP and CRTH2 in human nasal mucosa. Prostaglandins Other Lipid Mediat. 2004; 73:87–101.

21). Cao PP, Zhang YN, Liao B, Ma J, Wang BF, Wang H, et al. Increased local IgE production induced by common aeroallergens and phenotypic alteration of mast cells in Chinese eosinophilic, but not non-eosinophilic, chronic rhinosinusitis with nasal polyps. Clin Exp Allergy. 2014; 44:690–700.

22). Abonia JP, Blanchard C, Butz BB, Rainey HF, Collins MH, Stringer K, et al. Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol. 2010; 126:140–9.

23). Butterfield JH, Weiler CR. Prevention of mast cell activation disorder-associated clinical sequelae of excessive prostaglandin D(2) production. Int Arch Allergy Immunol. 2008; 147:338–43.

24). Diaz BL, Satake Y, Kikawada E, Balestrieri B, Arm JP. Group V secretory phospholipase A2 amplifies the induction of cyclooxygenase 2 and delayed prostaglandin D2 generation in mouse bone marrow culture-derived mast cells in a strain-dependent manner. Biochim Biophys Acta. 2006; 1761:1489–97.

25). Pettipher R. The roles of the prostaglandin D(2) receptors DP(1) and CRTH2 in promoting allergic responses. Br J Pharmacol. 2008; 153(Suppl 1):S191–9.

26). Xue L, Gyles SL, Wettey FR, Gazi L, Townsend E, Hunter MG, et al. Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. J Immunol. 2005; 175:6531–6.

27). Pettipher R, Whittaker M. Update on the development of antagonists of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). From lead optimization to clinical proof-of-concept in asthma and allergic rhinitis. J Med Chem. 2012; 55:2915–31.

28). Fajt ML, Gelhaus SL, Freeman B, Uvalle CE, Trudeau JB, Holguin F, et al. Prostaglandin D(2) pathway upregulation: relation to asthma severity, control, and TH2 inflammation. J Allergy Clin Immunol. 2013; 131:1504–12.

29). Fanning LB, Boyce JA. Lipid mediators and allergic diseases. Ann Allergy Asthma Immunol. 2013; 111:155–62.

30). Back M, Hansson GK. Leukotriene receptors in atherosclerosis. Ann Med. 2006; 38:493–502.