Human Mononuclear Cells and Neutral Proteinases. III. Neutral Proteinases and Rheumatoid Arthritis: Monocytes As a Source of Cathepsin G and Proteinase Potentiation of IgM Rheumatoid Factor Elaboration

Overview

Journal Inflammation

Specialties Allergy & Immunology
Pathology

Date 1989 Jun 1

PMID 2753524

Authors

R S Panush

Affiliations

Soon will be listed here.

Abstract

We have been interested in contributions of certain cells and mediators to synovial inflammation rheumatoid arthritis (RA). The present studies were designed to determine (1) whether monocytes contained the neutral proteinase cathepsin G and (2) if neutral proteinase could induce or potentiate cellular IgM rheumatoid factor (RF) production. Monocyte-rich and monocyte-poor populations were isolated by Ficoll-Hypaque density sedimentation followed by glass adherence, and cellular lysates were obtained by repetitive freezing and thawing as we have reported for neutrophil-derived neutral proteinase. Cathepsin G was quantified immunochemically by an enzyme-linked immunoassay (ELISA) we developed utilizing commercially available anti-cathepsin G antibodies. Mononuclear and B-cell-enriched cell cultures were prepared by standard methods and IgM RF measured by our ELISA. Cell-derived lysates from monocyte-enriched populations (84 +/- 3% monocytes, less than 1% neutrophils) contained considerably greater amounts of measurable cathepsin G (OD280 = 0.393 +/- 0.153) than lysates from equal numbers of monocyte (15 +/- 2% monocytes, less than 1% neutrophils)-depleted cells (OD280 = 0.071 +/- 0.038; P less than 0.05). Eighteen patients with RA and three normal individuals did not have consistently increased cellular elaboration of Ig or IgM RF in vitro in response to proteinase (trypsin) stimulation; however, patients manifested 80% potentiation by trypsin of pokeweed-stimulated cellular IgM RF production in vitro (pokeweed-stimulated IgM RF 137 +/- 53 ng/ml, pokeweed/trypsin-induced IgM RF 246 +/- 100 ng/ml; P less than 0.02), changes being most striking for those patients seropositive by latex fixation test (84% increase, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

References

Weissmann G, Spilberg I, Krakauer K . Arthritis induced in rabbits by lysates of granulocyte lysosomes. Arthritis Rheum. 1969; 12(2):103-16. DOI: 10.1002/art.1780120207. View

UNANUE E . Cooperation between mononuclear phagocytes and lymphocytes in immunity. N Engl J Med. 1980; 303(17):977-85. DOI: 10.1056/NEJM198010233031706. View

Panush R . Modulation of human mononuclear cell responses by neutrophil-derived factors. II. Partial characterization of a neutrophil-derived lymphocyte-enhancing factor (N-LEF). Inflammation. 1983; 7(1):35-47. DOI: 10.1007/BF00918006. View

Panush R, Katz P, Longley S . In vitro immunoglobulin production by mononuclear cells in rheumatoid arthritis. Clin Immunol Immunopathol. 1983; 28(2):252-64. DOI: 10.1016/0090-1229(83)90159-9. View

Nelson D . Macrophages: progress and problems. Clin Exp Immunol. 1981; 45(2):225-33. PMC: 1537385. View

UNANUE E . The regulatory role of macrophages in antigenic stimulation. Part Two: symbiotic relationship between lymphocytes and macrophages. Adv Immunol. 1981; 31:1-136. DOI: 10.1016/s0065-2776(08)60919-0. View

Rosenthal A . Regulation of the immune response--role of the macrophage. N Engl J Med. 1980; 303(20):1153-6. DOI: 10.1056/NEJM198011133032005. View

Schur P, Bianco N, Panush R . Antigammaglobulins in normal individuals and in patients with adult and juvenile rheumatoid arthritis and osteoarthritis. Rheumatology. 1975; 6:156-66. View

Goldstein I . Polymorphonuclear Leukocyte lysosomes and immune tissue injury. Prog Allergy. 1976; 20:301-40. View

10.

Yoshinaga M, Nishime K, Nakamura S, Goto F . A PMN-derived factor that enhances DNA-synthesis in PHA or antigen-stimulated lymphocytes. J Immunol. 1980; 124(1):94-9. View

11.

Hoch S, Schur P . Monocyte receptor function in patients with rheumatoid arthritis. Arthritis Rheum. 1981; 24(10):1268-7. DOI: 10.1002/art.1780241006. View

12.

Panush R . A new, simplified assay for suppressor cell function. J Clin Lab Immunol. 1982; 9(1):65-70. View

13.

Panush R . Nonspecific suppressor function in rheumatoid arthritis. J Clin Lab Immunol. 1982; 9(1):59-64. View

14.

Panush R . Modulation of human lymphocyte responses by neutrophil-derived factors: effects of neutrophils and neutrophil-derived factos. J Clin Lab Immunol. 1981; 5(2):113-20. View

15.

Saklatvala J, Barrett A . Identification of proteinases in rheumatoid synovium. Detection of leukocyte elastase cathepsin G and another serine proteinase. Biochim Biophys Acta. 1980; 615(1):167-77. DOI: 10.1016/0005-2744(80)90020-0. View

16.

Waytz P, Douglas S . Increased antibody-dependent cell-mediated cytotoxicity by monocytes from patients with rheumatoid arthritis. Arthritis Rheum. 1979; 22(5):490-4. DOI: 10.1002/art.1780220508. View

17.

Zembala M, Lemmel E . Inhibitory factor(s) of lymphoproliferation produced by synovial fluid mononuclear cells from rheumatoid arthritis patients: the role of monocytes in suppression. J Immunol. 1980; 125(3):1087-92. View

18.

Panush R, Bittner A, Sullivan M, Katz P, Longley S . IgM rheumatoid factor elaboration by blood, bone marrow, and synovial mononuclear cells in patients with rheumatoid arthritis. Clin Immunol Immunopathol. 1985; 34(3):387-91. DOI: 10.1016/0090-1229(85)90187-4. View

19.

Panush R, Bianco N, Schur P . Serum and synovial fluid IgG, IgA and IgM antigammaglobulins in rheumatoid arthritis. Arthritis Rheum. 1971; 14(6):737-47. DOI: 10.1002/art.1780140609. View

20.

Panush R . Monocytes in rheumatoid arthritis. Regulatory, effector, and phenotypic properties. J Rheumatol. 1985; 12(6):1053-61. View