title: Comparison of in vitro function of neutrophils from cattle deficient in plasma factor XI activity and from normal animals.
abstract: Cattle, homozygous for the genetic disorder of factor XI (FXI) deficiency, exhibit less than 2% of normal plasma FXI activity, display an increased bleeding tendency and are more prone to infectious diseases. FXI is one of the protein components of the contact activation system of coagulation that assembles on the surface of circulating neutrophils. Because of the central role of neutrophils in inflammation, the in vitro responses of neutrophils from normal and FXI deficient cattle were compared. Neutrophil degranulation was evaluated by measuring the release of myeloperoxidase and alkaline phosphatase, and the respiratory burst was evaluated by determining superoxide anion production. Neutrophils 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 derived from normal serum, the neutrophils from the FXI deficient animals exhibited a greater increase (P < 0.05) in both alkaline phosphatase release and superoxide production. In these neutrophils, following stimulation with C3b complement from normal serum, the relative increase in myeloperoxidase release compared to the unstimulated neutrophils was lower than that observed in the neutrophils from normal animals. There was minimal superoxide production in unactivated neutrophils from either normal or FXI deficient cattle and the response to phorbol ester stimulation was similar in both groups of animals. The C5a complement from FXI deficient serum was more effective (P < 0.05) in stimulating alkaline phosphatase release and superoxide production in normal neutrophils than the equivalent fraction from FXI deficient serum while the C3b complement from the FXI deficient serum was less effective than the normal serum fraction at inducing myeloperoxidase release from normal neutrophils. The results indicate that the differences in the in vitro neutrophil function are likely related to a variation in the function of the contact activation system on the neutrophil surface between normal and FXI deficient animals.
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Canada.
authors.forename: B L
authors.initials: BL
authors.lastname: Coomber
authors.forename: C L
authors.initials: CL
authors.lastname: Galligan
authors.forename: P A
authors.initials: PA
authors.lastname: Gentry
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015550:Cell Degranulation; D003179:Complement C3b / Q000378:metabolism; D015936:Complement C5a / Q000378:metabolism; D005173:Factor XI Deficiency / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D006720:Homozygote; D066298:In Vitro Techniques; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D016897:Respiratory Burst; D013481:Superoxides / Q000097:blood
chemical_list: D013481:Superoxides; D003179:Complement C3b; D015936:Complement C5a