Chemotaxis of rat mast cells toward adenine nucleotides

Rat mucosal mast cells express P2 purinoceptors, occupation of which mobili zes cytosolic Ca2+ and activates a potassium conductance, The primary funct ion of this P2 system in mast cell biology remains unknown. Here, we show t hat extracellular ADP causes morphological changes in rat bone marrow-cultu red mast cells (BMMC) typical of those occurring in cells stimulated by che motaxins, and that the nucleotides ADP, ATP and UTP are effective chemoattr actants for rat BMMC. ADP was also a chemotaxin for murine J774 monocytes, The nucleotide selectivity and pertussis toxin sensitivity of the rat BMMC migratory response suggest the involvement of P2U receptors, Poorly hydroly zable derivatives of ADP and ATP were effective chemotaxins, obviating a ro le for adenosine receptors, Buffering of external Ca2+ at 100 nM or reducti on of the electrical gradient driving Ca2+ entry (by elevating external K+) blocked ADP-driven chemotaxis, suggesting a role for Ca2+ influx in this p rocess. Anaphylatoxin C5a was a potent chemotaxin (EC50 approximate to 0.5 nM) for J774 monocytes, but it was inactive on rat BMMC in the presence or absence of laminin, Ca2+ removal or elevated [Kf] had modest effects on C5a -driven chemotaxis of J774 cells, implicating markedly different requiremen ts for Ca2+ signaling in C5a- vs ADP-mediated chemotaxis, This is supported by the observation that depletion of Ca2+ stores,vith thapsigargin complet ely blocked migration induced by ADP but not C5a, These findings suggest th at adenine nucleotides liberated from parasite-infested tissue could partic ipate in the recruitment of mast cells by intestinal mucosa.