Immunology Letters 68 (1999) 79 – 82 Inhibition of IgE-mediated triggering of mast cells by complement-derived peptides interacting with the FcRI Anna Erdei a,b, *, Ga ´bor K. To ´th c , Ma ´rton Andra ´sfalvy a , Ja ´nos Matko ´ d , La ´szlo ´ Bene d , Zsuzsa Bajtay a,b , Alexander Ischenko e , Xu Rong f , Israel Pecht f a Department of Immunology, Lora ´nd Eo ¨to ¨s Uniersity, Ja ´ orka Sa ´ndor u. 14, H-2131 Go ¨d, Hungary b Research Group of the Hungarian Academy of Sciences at the Department of Immunology, Lora ´nd Eo ¨to ¨s Uniersity, Go ¨d H-2131, Hungary c Department of Medical Chemistry, Szent -Gyo ¨rgyi Albert Medical School, Szeged, Hungary d Department of Biophysics and Cell Biology, Medical School, Debrecen, Hungary e Research Institute of Highly Pure Biochemicals, St. Petersburg, Russia f Department of Immunology, Weizmann Institute of Science, Rehoot 76100, Israel Abstract Mucosal type mast cells, in contrast to the serosal type ones, do not respond to cationic agents, or to the complement-derived peptides C3a and C5a [1]. Earlier we have found that while C3a does not activate the rat mucosal type mast cells (line RBL-2H3), it strongly inhibits the IgE-mediated triggering of these cells, by interfering with the FcRI-initiated signaling pathway [2]. In the present study we further investigated the mechanism of this process. It is shown, that C3a interacts with the -chain of the FcRI complex. Binding of the complement peptide to the cells apparently causes a decrease in the proximity of the IgE-binding FcRI. Investigating certain sequences of C3a we found that the inhibition is caused by the C-terminal sequences of the complement-pep- tide, ranging from positions 56 to 77 and also by a shorter sequence, ranging from positions 56 to 64. The inhibitory effect of these peptides was observed both in the case of RBL-2H3 cells and mouse bone marrow derived mast cells. © 1999 Elsevier Science B.V. All rights reserved. Keywords: Bone marrow derived mast cells; C3a; -chain of FcRI; Inhibition of IgE-mediated triggering; RBL-2H3 cells 1. Introduction The secretory response of mast cells and basophils is one of the most powerful effector mechanisms of the immune system. The allergic reaction develops upon activation of these cells, followed by the release of histamine or serotonin and other inflammatory media- tors including proteases, leukotriens and various cytoki- nes [3]. Mast cells and basophils can be activated by different stimuli. Triggering of these cells by clustering their FcRI and the cascade coupling it to the response are extensively studied [4 – 7]. Depending on the envi- ronment, mast cells mature from a common precursor into two types: the so-called serosal (or connective tissue type); and the mucosal type mast cells. The two phenotypes can be transdifferentiated; e.g. IL-3 is known to generate mucosal mast cells from rodent bone marrow, while fibroblast-derived factors cause a phenotypic change to the serosal type [1,3]. Both posses FcRI on their cell membrane, however they respond differently to secretagogues and inhibitors. The anaphy- latoxic activity of cationic peptides, including the com- plement-derived peptides C3a and C5a, has been known for a long time [1,8], however, it had also been shown that only serosal type mast cells can be activated by the so-called peptidergic stimuli, mucosal type ones are non-responsive [1]. Earlier we had shown that C3 a inhibits the IgE-mediated triggering of RBL-2H3 cells Abbreiations: BMMC, bone marrow derived mast cell; FRET, fluorescence resonance energy transfer. * Corresponding author. Tel.: +36-27-345311; fax: +36-27- 345147. E-mail address: erdann@alfa.elte.hu (A. Erdei) 0165-2478/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII:S0165-2478(99)00033-4