COMPARISON OF IN-VITRO FUNCTION OF NEUTROPHILS FROM CATTLE DEFICIENT IN PLASMA FACTOR-XI ACTIVITY AND FROM NORMAL ANIMALS

Cattle, homozygous for the genetic disorder of factor XI (FXI) deficie ncy, exhibit less than 2% of normal plasma FXI activity, display an in creased bleeding tendency and are more prone to infectious diseases. F XI is one of the protein components of the contact activation system o f coagulation that assembles on the surface of circulating neutrophils . Because of the central role of neutrophils in inflammation, the in v itro responses of neutrophils from normal and FXI deficient cattle wer e compared. Neutrophil degranulation was evaluated by measuring the re lease of myeloperoxidase and alkaline phosphatase, and the respiratory burst was evaluated by determining superoxide anion production. Neutr ophils from FXI deficient animals exhibited a significant increase (P < 0.05) in the spontaneous release of granule contents compared to the cells from normal cattle. Following stimulation with C5a complement d erived from normal serum, the neutrophils from the FXI deficient anima ls exhibited a greater increase(P < 0.05) in both alkaline phosphatase release and superoxide production. In these neutrophils, following st imulation with C3b complement from normal serum, the relative increase in myeloperoxidase release compared to the unstimulated neutrophils w as lower than that observed in the neutrophils from normal animals. Th ere was minimal superoxide production in unactivated neutrophils from either normal or FXI deficient cattle and the response to phorbol este r stimulation was similar in both groups of animals. The C5a complemen t from FXI deficient serum was more effective (P<0.05) in stimulating alkaline phosphatase release and superoxide production in normal neutr ophils than the equivalent fraction from FXI deficient serum while the C3b complement from the FXI deficient serum was less effective than t he normal serum fraction at inducing myeloperoxidase release from norm al neutrophils. The results indicate that the differences in the in vi tro neutrophil function are likely related to a variation in the funct ion of the contact activation system on the neutrophil surface between normal and FXI deficient animals. (C) 1997 Elsevier Science B.V.