Role of Mast Cells and C-Sensory Fibers in Concanavalin A-Induced Paw Edema in Two Rat Strains
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Role of Mast Cells and C-Sensory Fibers in Concanavalin A-Induced Paw Edema in Two Rat Strains Stanislava Stanojević,1,4 Nataša Kuštrimović,1,3 Katarina Mitić,1 Vesna Vujić,2 and Mirjana Dimitrijević1
Abstract—This study investigated a putative contribution of mast cells and C-sensory fibers to differences in the development of inflammatory edema following the injection of concanavalin A (Con A) into the hind paws of Dark Agouti (DA) and Albino Oxford (AO) rats. The treatment of adult rats with mast cell-depletor compound 48/80 and neonatal depletion of C-sensory fibers independently revealed that leukocyte composition of the inflamed paws and lymph nodes during local inflammatory response to Con A was generally regulated in a similar way in DA and AO rat strains. However, in DA and AO rats, the decrease and the increase of Con A-induced plasma extravasation were associated with mast cell depletion and activation, respectively, whereas neonatal capsaicin treatment activated dermal mast cells and potentiated inflammatory plasma extravasation only in adult rats of DA strain. Hence, strain differences in the development of the inflammatory response to Con A are probably controlled by the differences in the interplay between mast cells and C-sensory fibers in DA and AO rats. KEY WORDS: concanavalin A (Con A); paw edema; mast cells; C-sensory fibers; Dark Agouti (DA) and Albino Oxford (AO) rat strains.
INTRODUCTION The protein concanavalin A (Con A), a glycan-binding lectin isolated from the jack bean (Canavalia ensiformis) [1], has been widely used at lower doses (1–10 μg) as T cell mitogen in vitro [2]. At higher doses (200 μg), it was shown to stimulate T cell proliferation in vivo [3]. In contrast to other lectins from the Canavalia genus which exert systemic anti-inflammatory effects in different inflammatory models [4], Con A applied intraperitoneally promotes an intense accumulation of neutrophils, mononuclear cells, and mast cells in the rat peritoneal cavity [5, 6]. The in vitro treatment Institute of Virology, Vaccines and Sera BTorlak^, Immunology Research Center BBranislav Janković^, Vojvode Stepe 458, 11221 Belgrade, Serbia 2 Department of Chemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia 3 Present address: Department of Clinical and Experimental Pharmacology, University Insubria, Varese, Italia 4 To whom correspondence should be addressed at Institute of Virology, Vaccines and Sera BTorlak^, Immunology Research Center BBranislav Janković^, Vojvode Stepe 458, 11221 Belgrade, Serbia. E-mail: [email protected] 1
with Con A induces nitric oxide release and enhances the expression of Toll-like receptors 2–9 and their downstream signal transduction pathway molecules in macrophages [7, 8]. This treatment also upregulates cytokine content in peripheral blood mononuclear cells [9]. The intravitreal and intraplantar injections of Con A induce retinal and paw edema, respectively [10, 11], therefore making it a useful tool for studying the anti-inflammatory drugs. However, the Con A-induc
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