Surface immunoglobulins and protease inhibitors of human acute leukemia blasts

J. P. Cotropia, J. U. Gutterman, Evan M Hersh, G. M. Mavligit

Research output: Contribution to journalArticle

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Abstract

Cell-surface proteins of human leukemic blasts were studied by direct immunofluorescence (DIF), low pH elution and immunodiffusion (ID). Among AML blasts from 21 patients, the average proportions of blasts positive for IgG, IgM and IgA were 60%, 9% and 9% respectively. In contrast, blasts from 4 CML patients in blast crisis and 14 ALL patients had surface IgG, IgM and IgA values of 14%, 9% and 7% respectively for the former group and 1.4%, 1.1% and 0.8% respectively for the latter group. Blasts from 20 leukemic cell preparations were eluted at pH 2.4 for 30 min at 4°C in glycine. HC1 buffer. Immunodiffusion with appropriate specific antisera demonstrated intact IgG in 3 of 13 AML eluates. 10 of 13 AML eluates, 1 of 3 CML eluates, and 2 of 4 ALL eluates contained intact IgG and Fab fragment, but no Fc fragment. 1 CML eluate contained intact IgG; the remaining CML eluate contained Fab fragment only. 2 ALL eluates contained no IgG or fragments by double diffusion. An eluate from a pool of normal human leukocytes from 20 normal donors contained intact IgG and Fc fragment, but no Fab fragment. 19 of 20 leukemic cell eluates also contained the anti-proteases alpha-1-antitrypsin and alpha-1-anti-chymotrypsin which were shown to have been proteolytically modified. 5 of 20 leukemic cell eluates contained the anti-protease alpha-2-macroglobulin. The normal leukocyte eluate contained alpha-1-anti-trypsin but no alpha-1-anti-chymotrypsin or alpha-2-macroglobulin. The presence of Fab fragment in AML, CML blast crisis and ALL eluates suggests IgG binding by Fab as antibody, while Fc fragment in normal leukocyte eluate suggests binding via Fc to the Fc receptor. The expression of cell-associated proteolytic enzymes, as revealed by the presence of protease-modified anti-proteases, may explain cell-surface IgG degradation. A consequence of surface proteolytic activity would be the degradation of IgG antibody to yield Fab fragment bound to membrane antigenic determinants. The Fab reaction product is incapable of interacting with either complement or Fc receptors. Therefore, such proteolytic activity may protect the leukemic blasts from lysis by complement-dependent or antibody-dependent cell-mediated cytotoxic mechanisms.

Original languageEnglish (US)
Pages (from-to)520-531
Number of pages12
JournalInternational Journal of Cancer
Volume20
Issue number4
StatePublished - 1977
Externally publishedYes

Fingerprint

B-Cell Antigen Receptors
Protease Inhibitors
Leukemia
Immunoglobulin G
Immunoglobulin Fab Fragments
Immunoglobulin Fc Fragments
Peptide Hydrolases
Blast Crisis
Leukocytes
Fc Receptors
Immunodiffusion
Immunoglobulin A
Immunoglobulin M
Antibodies
alpha-Macroglobulins
Complement Receptors
Direct Fluorescent Antibody Technique
alpha 1-Antitrypsin
Chymotrypsin
Glycine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Surface immunoglobulins and protease inhibitors of human acute leukemia blasts. / Cotropia, J. P.; Gutterman, J. U.; Hersh, Evan M; Mavligit, G. M.

In: International Journal of Cancer, Vol. 20, No. 4, 1977, p. 520-531.

Research output: Contribution to journalArticle

Cotropia, JP, Gutterman, JU, Hersh, EM & Mavligit, GM 1977, 'Surface immunoglobulins and protease inhibitors of human acute leukemia blasts', International Journal of Cancer, vol. 20, no. 4, pp. 520-531.
Cotropia, J. P. ; Gutterman, J. U. ; Hersh, Evan M ; Mavligit, G. M. / Surface immunoglobulins and protease inhibitors of human acute leukemia blasts. In: International Journal of Cancer. 1977 ; Vol. 20, No. 4. pp. 520-531.
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N2 - Cell-surface proteins of human leukemic blasts were studied by direct immunofluorescence (DIF), low pH elution and immunodiffusion (ID). Among AML blasts from 21 patients, the average proportions of blasts positive for IgG, IgM and IgA were 60%, 9% and 9% respectively. In contrast, blasts from 4 CML patients in blast crisis and 14 ALL patients had surface IgG, IgM and IgA values of 14%, 9% and 7% respectively for the former group and 1.4%, 1.1% and 0.8% respectively for the latter group. Blasts from 20 leukemic cell preparations were eluted at pH 2.4 for 30 min at 4°C in glycine. HC1 buffer. Immunodiffusion with appropriate specific antisera demonstrated intact IgG in 3 of 13 AML eluates. 10 of 13 AML eluates, 1 of 3 CML eluates, and 2 of 4 ALL eluates contained intact IgG and Fab fragment, but no Fc fragment. 1 CML eluate contained intact IgG; the remaining CML eluate contained Fab fragment only. 2 ALL eluates contained no IgG or fragments by double diffusion. An eluate from a pool of normal human leukocytes from 20 normal donors contained intact IgG and Fc fragment, but no Fab fragment. 19 of 20 leukemic cell eluates also contained the anti-proteases alpha-1-antitrypsin and alpha-1-anti-chymotrypsin which were shown to have been proteolytically modified. 5 of 20 leukemic cell eluates contained the anti-protease alpha-2-macroglobulin. The normal leukocyte eluate contained alpha-1-anti-trypsin but no alpha-1-anti-chymotrypsin or alpha-2-macroglobulin. The presence of Fab fragment in AML, CML blast crisis and ALL eluates suggests IgG binding by Fab as antibody, while Fc fragment in normal leukocyte eluate suggests binding via Fc to the Fc receptor. The expression of cell-associated proteolytic enzymes, as revealed by the presence of protease-modified anti-proteases, may explain cell-surface IgG degradation. A consequence of surface proteolytic activity would be the degradation of IgG antibody to yield Fab fragment bound to membrane antigenic determinants. The Fab reaction product is incapable of interacting with either complement or Fc receptors. Therefore, such proteolytic activity may protect the leukemic blasts from lysis by complement-dependent or antibody-dependent cell-mediated cytotoxic mechanisms.

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