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Thrombin‐induced thromboxane generation by neutrophils and lymphocytes: Dependence on enzymic site

1987; Wiley; Volume: 132; Issue: 2 Linguagem: Inglês

10.1002/jcp.1041320224

1097-4652

Rena Bizios, Linda Lai, John W. Fenton, Asrar B. Malik,

Immune Response and Inflammation

Abstract We examined the effects of thrombin on thromboxane generation by sheep neutrophils and lymphocytes in vitro. Physiological concentration of thrombin (50 nM) resulted in thromboxane B 2 generation from both neutrophils and lymphocytes, which was comparable to that obtained with zymosan activated serum challenge of the cells. Thromboxane B 2 generation was dependent on the enzymic region of the thrombin molecule responsible for clotting activity because the complexing of thrombin with hirudin (1:1 U:U mixture of thrombin and hirudin) abolished thromboxane generation from both cell types. Further studies with modifed forms of α‐thrombin (which were produced by irreversible conjugation at the catalytic site and lacked enzymic activity) also showed no generation of thromboxane B 2 from neutrophils or lymphocytes. The results indicate that thrombin stimulates thromboxane generation from neutrophils and lymphocytes and that this response is dependent on the proteolytic activity of thrombin.