DIFFERENTIAL SUPEROXIDE ANION GENERATION BY EQUINE EOSINOPHILS AND NEUTROPHILS

Equine eosinophils and neutrophils are believed to play an important p ari in the protection of horses against parasitic and bacterial invasi on. Eosinophils may also play a key role in the pathogenesis of equine inflammatory conditions such as the allergic skin disease, insect hyp ersensitivity. The factors which stimulate the respiratory burst of eq uine eosinophils and neutrophils are poorly understood. The first aim of the present study was to determine the effects of the phorbol ester , phorbol myristate acetate (PMA), which is believed to activate intra cellular protein kinase C, and opsonised particles of serum-treated zy mosan (STZ), on the production of superoxide anions by equine eosinoph ils and neutrophils. Since histamine has been detected after antigen c hallenge in the skin of horses with insect hypersensitivity, the secon d aim was to establish the effects of this mediator on superoxide anio n production by equine eosinophils and the receptor sub-type(s) that m ediate histamine-induced responses. For comparison, responses of neutr ophils from the same horses were also examined. PMA and STZ induced si gnificant increases in superoxide anion generation by equine eosinophi ls and neutrophils. The estimated maximum (E-MAX) superoxide anion pro duction by eosinophils in the presence of PMA wassignificantly greater than that of neutrophils; the estimated concentration of PMA inducing 50% of the maximum response (EC50) by eosinophils was significantly l ess. The E-MAX values for superoxide anion production by neutrophils i n the presence of STZ were significantly greater than those for eosino phils. Histamine induced superoxide anion generation by equine eosinop hils which was inhibited by the histamine-1 receptor antagonists chlor pheniramine and mepyramine, but not the histamine-2 and histamine-3 re ceptor antagonists, cimetidine and thioperamide, respectively. Histami ne did not cause superoxide anion production by equine neutrophils. Th ese studies demonstrate that equine granulocytes vary in their ability to produce a respiratory burst in the presence of different stimuli, with eosinophils being more responsive to protein kinase C activators add neutrophils to opsonised particles. They also show that histamine selectively induced the generation of superoxide anions by equine eosi nophils via histamine-1 receptor activation. Thus, in horses with inse ct hypefsensitivity, histamine released from cutaneous mast cells afte r antigen challenge could activate eosinophils which have migrated int o the dermis. (C) 1997 Elsevier Science B.V.