Neutrophil Secretion During Blood Coagulation: Evidence for a Prekallikrein Independent Pathway

Summary

In association with blood coagulation, neutrophils undergo a secretory response (Plow, J Clin Invest 69: 564, 1982) and it has been suggested that plasma kallikrein is responsible for inducing this reaction (Wachtfogel et al., J Clin Invest 72: 1672, 1983). To assess the contribution of kallikrein to this response, the capacity of normal and prekallikrein-deficient blood and plasma to support secretion has been compared utilizing elastase as a marker of secretion. Serial dilutions of prekallikrein-deficient plasma were as effective as normal plasma in supporting neutrophil release of elastase. The extent of elastase release in spontaneously clotting normal and prekallikrein-deficient blood was similar. At 37° C in whole blood or at 22° C in plasma, prekallikrein activators had the same effect in neutrophil secretion in normal and prekallikrein-deficient blood and plasma samples. Taken together, these results provide evidence for the existence of a prekallikrein independent pathway that can function as a predominant mechanism for induction of neutrophil secretion during blood coagulation.

Keywords

Neutrophils - Prekallikrein - Elastase

• References

• 1 Plow EF. The major fibrinolytic proteases of human leukocytes. Biochim Biophys Acta 1980; 63: 47-56
• 2 Plow EF. Leukocyte elastase release during blood coagulation. J Clin Invest 1982; 69: 564-572
• 3 Brower MS, Harpel PC. Alpha-1-antitrypsin-human leukocyte elastase complexes in blood: quantification by an enzyme-linked differential antibody immunosorbed assay and comparison with alpha-2-plasmin inhibitor-plasmin complexes. Blood 1983; 61: 842-849
• 4 Plow EF, Edgington TS. An alternative pathway for fibrinolysis. J Clin Invest 1975; 56: 30-38
• 5 Plow EF. The contribution of leukocyte proteases to fibrinolysis. Blut 1986; 53: 01-09
• 6 Egbring R, Schmidt W, Fuchs G, Havemann K. Demonstration of granulocytic proteases in plasma of patients with acute leukemia and septicemia with coagulation defects. Blood 1977; 49: 219-231
• 7 Plow EF, Gramse M, Havemann K. Immunochemical discrimination of leukocyte elastase from plasmic degradation products of fibrinogen. J Lab Clin Med 1983; 102: 858-869
• 8 Weitz JI, Landman SL, Crowley KA, Birken S. Development of an assay for in vivo human neutrophil elastase activity. J Clin Invest 1986; 78: 155-162
• 9 Wachtfogel YT, Kucich U, James HL, Scott CF, Shapira M, Zimmerman M, Cohen AB, Colman RW. Human plasma kallikrein releases neutrophil elastase during blood coagulation. J Clin Invest 1983; 72: 1672-1677
• 10 Shapira M, Despland E, Scott CF, Boxer LA, Coleman RW. Purified human plasma kallikrein aggregates human blood neutrophils. J Clin Invest 1982; 69: 1199-1202
• 11 Colman RW, Wachtfogel YT, Kucich U, Weinbaum G, Hahn S, Pixley RA, Scott CF, deAgostini A, Burger D, Shapira M. Effect of cleavage of the heavy chain of human plasma kallikrein on its functional properties. Blood 1985; 65: 311-318
• 12 Fisher CA, Schmaier AH, Addonizio VP, Colman RW. Assay of prekallikrein in human plasma: comparison of amidolytic, esterolytic, coagulation and immunochemical Assays. Blood 1982; 59: 963-970
• 13 Harpel PC, Lewin MF, Kaplan AP. Distribution of plasma kallikrein between Cl inactivator and α₂-macroglobulin in plasma utilizing a new assay for α₂-macroglobulin-kallikrein complexes. J Biol Chem 1985; 260: 4257-4263
• 14 Plow EF, Plescia J. Non-plasmin mediated fibrinolysis. In: Progress in Fibrinolysis. vol. 5 Davidson JF, Nilsson IM, Asteits B. (eds) Churchill-Livingstone; Edinburgh: 1981. p 70