Increased cytosolic calcium in cystic fibrosis neutrophils effect on stimulus - secretion coupling

A disorder of calcium homeostasis has been related to the pathogenesis of Cystic Fibrosis (CF). The Authors have studied the relationship between the cytosolic free calcium concentration ([Ca 2+]i), the amount of Ca 2+ released from endogeneous stores and the secretory response in CF neutrophils. Significantly elevated resting [Ca 2+]i and depressed Ca 2+ release induced by the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) is present in CF neutrophils. In the absence of exogenous Ca 2+ the secretory response of CF neutrophils after a weak stimulus such as Cytochalasin B (CB) is greater than in normal neutrophils, while a depressed secretion of azurophilic granules is evident in CF neutrophils stimulated by CB + FMLP. The data confirm the hypothesis of an altered Ca 2+ homeostasis in CF cells. Cystic Fibrosis (CF), an autosomal recessive exocrinopathy, is characterized by secretory abnormalities and ion transport dysfunction (for review see 1, 2). Since intracellular Ca 2+ seems to play a role in stimulus-secretion coupling and ion movements, several aspects of Ca 2+ homeostasis have been investigated in CF. The total Ca 2+ content has been reported to be increased in fibroblast cultures and in lymphocytes (3,4,5) and mitochondrial Ca 2+ uptake was found elevated in fibroblast cultures (6). An elevated free cytosolic calcium concentration ([Ca 2+]i) has been recently reported in buccal epithelial cells (7), while normal concentration has been found in lymphocytes and Epstein Barr virus transformed lymphoblasts (5,8). The present paper shows the results of a study in human neutrophils, a cell whose several functions such as secretion, movement and respiratory burst are in some way regulated by Ca 2+. The data report that in neutrophils of CF patients the resting [Ca 2+]i is higher and the secretory response is partly modified.