This paper is only available as a PDF. To read, Please Download here.
Abstract
This investigation sought to determine the effect of trypsin-kallikrein (T-K) inhibitor
upon the inflammatory reaction induced by urate crystals in rabbits. Sodium urate
crystals were injected into the skin and joints of rabbits. The resulting inflammatory
response was substantially lessened when the T-K inhibitor was also injected. In vitro
testing shows that the T-K inhibitor greatly reduced the proteolytic activity of polymorphonuclear
lysosomal lysates at acid and neutral pH. Complement depletion of rabbits did not
alter the joint inflammation resulting from injection of microcrystalline urate. It
is suggested that the observed anti-inflammatory properties of the T-K inhibitor are
related to its ability to inhibit acid and neutral polymorpho-nuclear lysosomal proteases
and, to a lesser degree, to inhibition of kinin-forming enzymes. The evidence is reviewed
which suggests that the proteases may be a major mediator of the inflammatory response
in this model.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Translational ResearchAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Studies in the nature of gouty tophi.Deutsch. Arch. Klin. Med. 1899; 63: 266
- Ann. Intern. Med. 1964; 60 (an abridged translation with comments by Bull, J. M., and McCarty, D. J., Jr.): 486
- Fate and effects of the acid uric acid sodium in the abdominal and joint cavities of the rabbit.Deutsch. Arch. Klin. Med. 1900; 67: 81
- The identification of urate crystals in gouty synovial fluid.Ann. Intern. Med. 1961; 54: 452
- Acute arthritis in man and dog after intrasynovial injection of sodium urate crystals.Lancet. 1962; 2: 682
- The inflammatory response to injected sodium urate.J. A. M. A. 1962; 180: 469
- Hageman factor and acute gouty arthritis.Arthritis Rheum. 1968; 11: 452
- Kinins and arthritis.Bull. Rheum. Dis. 1968; 19: 512
- Possible implication of complement in acute gout.J. Clin. Invest. 1967; 46 (Abst.): 1099
- Crystal-induced inflammation in canine joints. II. Importance of polymorphonuclear leukocytes.J. Exp. Med. 1966; 124: 115
- Suppression of urate crystal-induced canine joint inflammation by heterologous anti-polymorphonuclear leukocyte serum.Arthritis Rheum. 1968; 11: 145
- Lysosomes and gout.Nature. 1966; 210: 959
- Proteases in inflammation.Ann. N. Y. Acad. Sci. 1968; 146: 527
- Trasylol.Biochem. Pharmacol. 1969; 16: 59
- Crystal-induced arthritis.Postgrad. Med. 1969; 45: 87
- Isolation and properties of specific cytoplasmic granules of rabbit polymorphonuclear leukocytes.J. Exp. Med. 1960; 112: 983
- The estimation of cathepsin with hemoglobin and the partial purification of cathepsin.J. Gen. Physiol. 1938; 22: 79
- Diagnostic complement fixation. I. A method.Amer. J. Syph. 1952; 36: 2
- A new concept of immunosuppression in hypersensitivity reactions and in transplantation immunity.Survey Ophthal. 1966; 11: 498
- Elastolysis by human leukocyte granules.J. Exp. Med. 1968; 128: 1137
- Lysosomes and joint disease.Arthritis Rheum. 1966; 9: 934
- Arthritis induced in rabbits by lysates of granulocyte lysosomes.Arthritis Rheum. 1969; 12: 103
- Polymorphonuclear leukocyte motility in vitro. III. Possible release of a chemotactic substance after phagocytosis of urate crystals by polymorphonuclear leukocytes.Arthritis Rheum. 1969; 12: 197
- The kinin-forming and kinidase activities of rabbit polymorphonuclear leukocytes.Brit. J. Pharmacol. 1967; 29: 238
- The presence of a kinin peptide in inflammatory synovial effusions.Arthritis Rheum. 1964; 7 (Abst.): 311
- Crystal induced inflammation in canine joints. III. Evidence against bradykinin as a mediator of inflammation.J. Lab. Clin. Med. 1966; 68: 433
- Blocking of the in vivo effects of bradykinin and kallekrein with carboxypeptidase B.J. Pharmacol. Exp. Ther. 1963; 142: 327
- Chemotaxis of polymorphonuclear leukocytes.Biochem. Pharmaeol. 1968; 17 (Suppl.): 99
- Complement as a mediator of inflammation. III. Purification of the activity with anaphylatoxic properties generated by interaction of the first four components of complement and its identification as a cleavage product of C′3.J. Exp. Med. 1967; 126: 102
- Two anticomplementary factors in cobra venom: Hemolysis of guinea pig erythrocytes by one of them.J. Immun. 1969; 103: 944
Article info
Publication history
Accepted:
July 8,
1970
Received:
December 5,
1969
Footnotes
☆Supported by Grant T1 AM 5548 from the National Institutes of Health and a grant from the John A. Hartford Foundation.
Identification
Copyright
© 1970 Published by Elsevier Inc.