Antibacterial activity of cationic proteins from human granulocytes.
PDF (1.2M)
Journal: 1976/January - Journal of Clinical Investigation
ISSN: 0021-9738
Abstract:
Human granulocytes contain several cationic proteins with a molecular weight of approximately 25,000, almost identical amino acid composition, and complete immunologic identity. These proteins possess a chymotrypsin-like protease activity at a neutral pH. The antibacterial activity of the cationic proteins has been studied. Bactericidal activities are found against both Gram-positive (Streptococcus faecalis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) organisms. Gram-positive bacteria are, however, the most sensitive. The pH-optimum is near neutrality, and the microbicidal activity shows an inverse relationship to the ionic strength, indicating an ionic interaction between the cationic proteins and the bacterial surface. The microbicidal effect of the cationic proteins is generally independent of the chymotrypsin-like activity of the same proteins since the activity against several bacterial species is heat stable while the chymotrypsin-like activity is heat labile. The surface properties of S. aureus that are determined by protein A do not seem to influence the susceptibility to cationic proteins. The properties of the Gram-negative envelope of E. coli that determine the susceptibility to the lytic action of serum do not influence the sensitivity to the action of cationic proteins. The present study shows that cationic proteins of human granulocytes represent one potential microbicidal mechanism that is independent of hydrogen peroxide and myeloperoxidase.
Open in
PUBMED | DOI | PMC | Google Scholar | Wikipedia
Relations:
Content
Citations
(56)
References
(33)
Chemicals
(1)
Organisms
(3)
Processes
(3)
Anatomy
(2)
Similar articles
Articles by the same authors
Discussion board
J Clin Invest 56(5): 1118-1124
PMID: 241758

Antibacterial activity of cationic proteins from human granulocytes.

Abstract

Human granulocytes contain several cationic proteins with a molecular weight of approximately 25,000, almost identical amino acid composition, and complete immunologic identity. These proteins possess a chymotrypsin-like protease activity at a neutral pH. The antibacterial activity of the cationic proteins has been studied. Bactericidal activities are found against both Gram-positive (Streptococcus faecalis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) organisms. Gram-positive bacteria are, however, the most sensitive. The pH-optimum is near neutrality, and the microbicidal activity shows an inverse relationship to the ionic strength, indicating an ionic interaction between the cationic proteins and the bacterial surface. The microbicidal effect of the cationic proteins is generally independent of the chymotrypsin-like activity of the same proteins since the activity against several bacterial species is heat stable while the chymotrypsin-like activity is heat labile. The surface properties of S. aureus that are determined by protein A do not seem to influence the susceptibility to cationic proteins. The properties of the Gram-negative envelope of E. coli that determine the susceptibility to the lytic action of serum do not influence the sensitivity to the action of cationic proteins. The present study shows that cationic proteins of human granulocytes represent one potential microbicidal mechanism that is independent of hydrogen peroxide and myeloperoxidase.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
icon of scanned page 1118
1118
icon of scanned page 1119
1119
icon of scanned page 1120
1120
icon of scanned page 1121
1121
icon of scanned page 1122
1122
icon of scanned page 1123
1123
icon of scanned page 1124
1124

Images in this article

Image
Image
on p.1119
Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Klebanoff SJ. Myeloperoxidase: contribution to the microbicidal activity of intact leukocytes. Science. 1970 Sep 11;169(3950):1095–1097. [PubMed] [Google Scholar]
  • Elsbach P. On the interaction between phagocytes and micro-organisms. N Engl J Med. 1973 Oct 18;289(16):846–852. [PubMed] [Google Scholar]
  • Holmes B, Page AR, Good RA. Studies of the metabolic activity of leukocytes from patients with a genetic abnormality of phagocytic function. J Clin Invest. 1967 Sep;46(9):1422–1432.[PMC free article] [PubMed] [Google Scholar]
  • Kaplan EL, Laxdal T, Quie PG. Studies of polymorphonuclear leukocytes from patients with chronic granulomatous disease of childhood: bactericidal capacity for streptococci. Pediatrics. 1968 Mar;41(3):591–599. [PubMed] [Google Scholar]
  • Klebanoff SJ, White LR. Iodination defect in the leukocytes of a patient with chronic granulomatous disease of childhood. N Engl J Med. 1969 Feb 27;280(9):460–466. [PubMed] [Google Scholar]
  • Mandell GL, Hook EW. Leukocyte function in chronic granulomatous disease of childhood. Studies on a seventeen year old boy. Am J Med. 1969 Sep;47(3):473–486. [PubMed] [Google Scholar]
  • Lehrer RI, Cline MJ. Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection. J Clin Invest. 1969 Aug;48(8):1478–1488.[PMC free article] [PubMed] [Google Scholar]
  • Lehrer RI, Hanifin J, Cline MJ. Defective bactericidal activity in myeloperoxidase-deficient human neutrophils. Nature. 1969 Jul 5;223(5201):78–79. [PubMed] [Google Scholar]
  • HIRSCH JG. Further studies on preparation and properties of phagocytin. J Exp Med. 1960 Mar 1;111:323–337.[PMC free article] [PubMed] [Google Scholar]
  • Zeya HI, Spitznagel JK. Antimicrobial specificity of leukocyte lysosomal cationic proteins. Science. 1966 Nov 25;154(3752):1049–1051. [PubMed] [Google Scholar]
  • Olsson I, Venge P. Cationic proteins of human granulocytes. II. Separation of the cationic proteins of the granules of leukemic myeloid cells. Blood. 1974 Aug;44(2):235–246. [PubMed] [Google Scholar]
  • Rindler R, Braunsteiner H. Soluble proteins from human leukocyte granules. I. Esterase activity of cationic proteins. Blut. 1973 Jul;27(1):26–32. [PubMed] [Google Scholar]
  • Arvidson S, Holme T, Wadström T. Influence of cultivation conditions on the production of extracellular proteins by Staphylococcus aureus. Acta Pathol Microbiol Scand B Microbiol Immunol. 1971;79(3):399–405. [PubMed] [Google Scholar]
  • Odeberg H, Olsson I, Venge P. Cationic proteins of human granulocytes. IV. Esterase activity. Lab Invest. 1975 Jan;32(1):86–90. [PubMed] [Google Scholar]
  • Ranadive NS, Cochrane CG. Isolation and characterization of permeability factors from rabbit neutrophils. J Exp Med. 1968 Oct 1;128(4):605–622.[PMC free article] [PubMed] [Google Scholar]
  • Zeya HI, Spitznagel JK. Cationic proteins of polymorphonuclear leukocyte lysosomes. II. Composition, properties, and mechanism of antibacterial action. J Bacteriol. 1966 Feb;91(2):755–762.[PMC free article] [PubMed] [Google Scholar]
  • HIRSCH JG. Bactericidal action of histone. J Exp Med. 1958 Dec 1;108(6):925–944.[PMC free article] [PubMed] [Google Scholar]
  • Penniall R, Zeya HI. The effects of cationic proteins of rabbit polymorphonuclear leukocyte lysosomes on the respiratory activity of liver mitochondria. Biochem Biophys Res Commun. 1971 Oct 1;45(1):6–13. [PubMed] [Google Scholar]
  • Babior BM, Kipnes RS, Curnutte JT. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973 Mar;52(3):741–744.[PMC free article] [PubMed] [Google Scholar]
  • Mandell GL. Bactericidal activity of aerobic and anaerobic polymorphonuclear neutrophils. Infect Immun. 1974 Feb;9(2):337–341.[PMC free article] [PubMed] [Google Scholar]
  • Lehrer RI. Functional aspects of a second mechanism of candidacidal activity by human neutrophils. J Clin Invest. 1972 Oct;51(10):2566–2572.[PMC free article] [PubMed] [Google Scholar]
  • Shohet SB, Pitt J, Baehner RL, Poplack DG. Lipid peroxidation in the killing of phagocytized pneumococci. Infect Immun. 1974 Dec;10(6):1321–1328.[PMC free article] [PubMed] [Google Scholar]
  • Jensen MS, Bainton DF. Temporal changes in pH within the phagocytic vacuole of the polymorphonuclear neutrophilic leukocyte. J Cell Biol. 1973 Feb;56(2):379–388.[PMC free article] [PubMed] [Google Scholar]
  • Mandell GL. Intraphagosomal pH of human polymorphonuclear neutrophils. Proc Soc Exp Biol Med. 1970 Jun;134(2):447–449. [PubMed] [Google Scholar]
  • Ohlsson K, Olsson I. The neutral proteases of human granulocytes. Isolation and partial characterization of granulocyte elastases. Eur J Biochem. 1974 Mar 1;42(2):519–527. [PubMed] [Google Scholar]
  • Ohlsson K, Olsson I. The neutral proteases of human granulocytes. Isolation and partial characterization of two granulocyte collagenases. Eur J Biochem. 1973 Jul 16;36(2):473–481. [PubMed] [Google Scholar]
  • Baggiolini M, Hirsch JG, De Duve C. Resolution of granules from rabbit heterophil leukocytes into distinct populations by zonal sedimentation. J Cell Biol. 1969 Feb;40(2):529–541.[PMC free article] [PubMed] [Google Scholar]
  • Bainton DF, Ullyot JL, Farquhar MG. The development of neutrophilic polymorphonuclear leukocytes in human bone marrow. J Exp Med. 1971 Oct 1;134(4):907–934.[PMC free article] [PubMed] [Google Scholar]
  • Zeya HI, Spitznagel JK. Characterization of cationic protein-bearing granules of polymorphonuclear leukocytes. Lab Invest. 1971 Mar;24(3):229–236. [PubMed] [Google Scholar]
  • Spitznagel JK, Dalldorf FG, Leffell MS, Folds JD, Welsh IR, Cooney MH, Martin LE. Character of azurophil and specific granules purified from human polymorphonuclear leukocytes. Lab Invest. 1974 Jun;30(6):774–785. [PubMed] [Google Scholar]
  • Dewald B, Rindler-Ludwig R, Bretz U, Baggiolini M. Subcellular localization and heterogeneity of neutral proteases in neutrophilic polymorphonuclear leukocytes. J Exp Med. 1975 Apr 1;141(4):709–723.[PMC free article] [PubMed] [Google Scholar]
  • Bainton DF. Sequential degranulation of the two types of polymorphonuclear leukocyte granules during phagocytosis of microorganisms. J Cell Biol. 1973 Aug;58(2):249–264.[PMC free article] [PubMed] [Google Scholar]
  • Leffell MS, Spitznagel JK. Intracellular and extracellular degranulation of human polymorphonuclear azurophil and specific granules induced by immune complexes. Infect Immun. 1974 Dec;10(6):1241–1249.[PMC free article] [PubMed] [Google Scholar]
Copyright notice
Abstract
Human granulocytes contain several cationic proteins with a molecular weight of approximately 25,000, almost identical amino acid composition, and complete immunologic identity. These proteins possess a chymotrypsin-like protease activity at a neutral pH. The antibacterial activity of the cationic proteins has been studied. Bactericidal activities are found against both Gram-positive (Streptococcus faecalis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) organisms. Gram-positive bacteria are, however, the most sensitive. The pH-optimum is near neutrality, and the microbicidal activity shows an inverse relationship to the ionic strength, indicating an ionic interaction between the cationic proteins and the bacterial surface. The microbicidal effect of the cationic proteins is generally independent of the chymotrypsin-like activity of the same proteins since the activity against several bacterial species is heat stable while the chymotrypsin-like activity is heat labile. The surface properties of S. aureus that are determined by protein A do not seem to influence the susceptibility to cationic proteins. The properties of the Gram-negative envelope of E. coli that determine the susceptibility to the lytic action of serum do not influence the sensitivity to the action of cationic proteins. The present study shows that cationic proteins of human granulocytes represent one potential microbicidal mechanism that is independent of hydrogen peroxide and myeloperoxidase.
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.