Calcium (Ca2+) is important in mast cell-pathway activation

Al. Caraffa

School of Pharmacy, University of Camerino, Camerino, Italy

Mast cells (MCs) are hematopoietic cells derived from hematopoietic bone-marrow progenitor cells. Mature MCs normally reside in virtually all vascularized tissues. MC activation via IgE-induced cross-linking of FcRI involves the stimulation of several enzymes including phospholipase Cg (PLCg) which regulates intracellular calcium (Ca²⁺) release and protein kinase (PKC) activity by hydrolyzing phosphatidyl inositol biphosphate to form IP₃ and dyacyl glycerol (DAG). The activation of GTPases leads to mitogen-activated protein kinase (MAPK) c-Jun kinase (JNK) and protein 38 (p38) which regulate the transcription factors for the production of pro-inflammatory cytokines. The response of MCs to antigens consists of the exstracellular release of preformed mediators stored in the cytoplasmatic granules of the cells, and the de novo synthesis of pro-inflammatory cytokines/chemokines. Upon appropriate MC activation (IgE) they produce pro-inflammatory mediators. The cross-linking of their receptor Fce-RI-bound IgE initiates the activation. The stored preformed mediators consist of histamine, tryptase, bradykinin, CRH, SP, heparin hyaluronic acid and orhers; while de novo synthesis consists of cytokines and lipid mediators (prostaglandin and leukotrienes).