α2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis

Nathan Kaufman, Jimmy D. Page, Robin A. Pixley, Roland Schein, Alvin H. Schmaier, Robert W. Colman

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Activation of the contact system has been documented in severe sepsis and hereditary angioedema, but a sensitive, specific, and quantitative assay for assessing the degree of involvement of this proteolytic enzyme cascade is not yet available. We have developed a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) for the α2-macroglobulin-kallikrein (α2M-Kal) complex using an F(ab′)2 derivative of a monospecific polyclonal antibody against α2M as the capture antibody and a unique murine monoclonal antibody, 13G11, against the heavy chain of kallikrein as the detector antibody. The assay does not detect complexes in normal plasma but reacts with complexes generated by activating normal plasma with dextran sulfate at 4°C in a range of 5 to 375 nmol/L. A close correlation of the ELISA with an amidolytic assay for α2M-Kal was documented. Patients with sepsis syndrome but negative bacterial blood cultures did not show elevated plasma complexes, whereas a majority of those with positive blood cultures did show modest elevation and a single patient with septic shock showed a very high level of α2M-Kal complex. Similarly, a patient with classic hereditary angioedema (HAE) showed increased concentration of complexes on three separate occasions during attacks but normal levels between attacks. Two other HAE patients did not show elevated levels at quiescent periods. The ELISA for α2M-Kal appears to be sensitive, specific, and quantitative, and it can be used to reflect the degree of contact system activation in human sepsis and in HAE attacks.

Original languageEnglish
Pages (from-to)2660-2667
Number of pages8
JournalBlood
Volume77
Issue number12
StatePublished - Jun 15 1991
Externally publishedYes

Fingerprint

Hereditary Angioedemas
Tissue Kallikreins
Macroglobulins
Kallikreins
Assays
Sepsis
Chemical activation
Immunosorbents
Enzyme-Linked Immunosorbent Assay
Antibodies
Plasmas
Systemic Inflammatory Response Syndrome
Dextran Sulfate
Blood
Enzymes
Septic Shock
Peptide Hydrolases
Monoclonal Antibodies
Derivatives
Detectors

ASJC Scopus subject areas

  • Hematology

Cite this

Kaufman, N., Page, J. D., Pixley, R. A., Schein, R., Schmaier, A. H., & Colman, R. W. (1991). α2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis. Blood, 77(12), 2660-2667.

α2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis. / Kaufman, Nathan; Page, Jimmy D.; Pixley, Robin A.; Schein, Roland; Schmaier, Alvin H.; Colman, Robert W.

In: Blood, Vol. 77, No. 12, 15.06.1991, p. 2660-2667.

Research output: Contribution to journalArticle

Kaufman, N, Page, JD, Pixley, RA, Schein, R, Schmaier, AH & Colman, RW 1991, 'α2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis', Blood, vol. 77, no. 12, pp. 2660-2667.
Kaufman N, Page JD, Pixley RA, Schein R, Schmaier AH, Colman RW. α2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis. Blood. 1991 Jun 15;77(12):2660-2667.
Kaufman, Nathan ; Page, Jimmy D. ; Pixley, Robin A. ; Schein, Roland ; Schmaier, Alvin H. ; Colman, Robert W. / α2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis. In: Blood. 1991 ; Vol. 77, No. 12. pp. 2660-2667.
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