No abstract

Cathelicidins represent a family of cationic peptides involved in host defense systems. Apart from exerting direct anti-microbial effects, cathelicidins can regulate immune responses by affecting the activity of cells playing a role in antibacterial defense. Taking into account that mast cells are critical components of host defense, the aim of this study was to determine whether rat cathelicidin-related anti-microbial peptide (rCRAMP) can influence mast cell activity. We have demonstrated that activation of fully mature rat mast cells with rCRAMP resulted in generation and release of cysteinyl leukotrienes (cysLTs). However, rCRAMP failed to induce mast cell degranulation and histamine release. We also found that rCRAMP stimulated rat mast cells to synthesize TNF, but not CXCL8. What is more, this peptide induced GM-CSF, IL-1β, CCL2 and CCL3 but not IL-33 mRNA expression in mast cells. Finally, we showed that this cathelicidin serves as potent chemoattractant for rat mast cells. rCRAMP-mediated cysLT synthesis and mast cell migration were strongly inhibited by IL-10 pre-treatment. With the use of specific inhibitors, we established that activation of PLC/A2 and ERK1/2, but not p38, was required for rCRAMP-induced mast cell stimulation, while PI3K-dependent pathway is involved in both TNF synthesis and mast cell migration. Our results suggest that cathelicidins can amplify inflammatory responses by causing mast cells accumulation and by stimulating these cells to release potent pro-inflammatory mediators.

Mast cells play an important role in diverse physiological mechanisms as well as taking part in antimicrobial defense. What is more, these cells are important regulators of a number of pathophysiological processes, involving allergic reactions. Therefore, it seems to be very important to know and understand the factors and receptors influencing mast cell activity. Nowadays it is well established that activating signals are counterbalanced by negative or inhibition signals transmitted by inhibitory receptors containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Inhibitory receptor engagement leads to ITIM tyrosine phosphorylation, the recruitment and activation of protein tyrosine phosphatases such as SHP-1, SHP-2 and/or SHIP, and the dephosphorylation of activating receptor associated proteins. There is growing evidence that a number of inhibitory receptors have been identified on mast cells. The scope of this paper is to present the current knowledge on mast cell-associated inhibitory receptors, such as FcγRIIB, paired immunoglobulin-like receptor B (PIR-B), CD300, CD172a, gp49B1, CD200R, sialic acid-binding immunoglobulin-like lectin (Siglec) molecules, CD305, allergin-1, mast cell function-associated antigen (MAFA), and CD72. The role of these inhibitory receptors in regulation mast cell activity is also discussed.

The aim of study was to compare the potency of different bacterial antigens to induce rat mature mast cell to cysteinyl leukotriene (cysLT) generation. We examined Toll-like receptor (TLR)2 agonists, i.

Mast cells play an important role in many physiological