Download PDF
Thromb Haemost 1994; 72(01): 054-057
DOI: 10.1055/s-0038-1648810
Original Article
Schattauer GmbH Stuttgart

Increased Mononuclear Cell Tissue Factor and Type-2 Plasminogen Activator Inhibitor and Reduced Plasma Fibrinolytic Capacity in Children with Lymphoma

N Semeraro
The Dipartimento di Scienze Biomediche e Oncologia Umana Sezione di Patologia Generale, Italy
,
P Montemurro
The Dipartimento di Scienze Biomediche e Oncologia Umana Sezione di Patologia Generale, Italy
,
P Giordano
*   Dipartimento di Biomedicina dell’età evolutiva, Clinica Pediatrica, Università di Bari, Bari, Italy
,
N Santoro
*   Dipartimento di Biomedicina dell’età evolutiva, Clinica Pediatrica, Università di Bari, Bari, Italy
,
D De Mattia
*   Dipartimento di Biomedicina dell’età evolutiva, Clinica Pediatrica, Università di Bari, Bari, Italy
,
M Colucci
The Dipartimento di Scienze Biomediche e Oncologia Umana Sezione di Patologia Generale, Italy
› Author Affiliations
Further Information

Publication History

Received 25 January 1994

Accepted after revision 24 March 1994

Publication Date:
12 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Blood clotting activation and fibrin deposition are common findings in lymphoma patients. We evaluated the capacity of peripheral blood mononuclear cells to produce procoagulant activity (PCA) and plasminogen activator inhibitor (PAI) in 12 children with newly diagnosed lymphoma (8 non-Hodgkin’s, 4 Hodgkin’s) and in 12 matched healthy donors. In the same subjects we also measured plasma antigen levels of tissue-type PA (t-PA), urokinase-type PA (u-PA), PAI-1, PAI-2, and D-dimer. PCA generated by mononuclear cells after incubation for 20 h at 37° C was significantly higher in patients than in controls (p = 0.027). In all samples it was identified as tissue factor by functional criteria (dependence on factor VII). Moreover, culture medium obtained from patients’ mononuclear cells after incubation for 20 h at 37° C contained significantly higher amounts of PAI activity and PAI-2 antigen than control samples (p <0.001). Plasma PAI-1 and t-PA antigens were significantly augmented in patients (p <0.005), the mean increase of PAI-I being about 5 times higher than that of t-PA. Plasma levels of D-dimer wete markedly increased in the patients’ group (p <0.001), whereas u-PA and PAI-2 antigens did not differ from controls. It is suggested that monocytes from lymphoma patients are endowed with functional abnormalities leading to the simultaneous expression of tissue factor and antifibrinolytic activity. These abnormalities, coupled with a reduced plasma fibrinolytic potential, could play an important pathogenetic role in blood clotting activation and fibrin deposition associated with lymphoma.

 

  • References

  • 1 Harris NL, Dvorak AM, Smith J, Dvorak HF. Fibrin deposits in Hodgkin’s disease. Am J Pathol 1982; 108: 119-129
    PubMedGoogle Scholar
  • 2 Muszbek L, Adany R. Intratumoral fibrin stabilization. In: Eicosanoids, lipid peroxidation and cancer Nigam SK, McBrien DCH, Slater TF. eds. Springer-Verlag, New York: 1988: 339-349
  • 3 Adany R, Kappelmayer J, Berenyi E, Szegeda A, Fabian E, Muszbek L. Factors of the extrinsic pathway of blood coagulation in tumor associated macrophages. Thromb Haemost 1989; 62: 850-855
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Costantini V, Zacharski LR, Memoli VA, Kisiel W, Kudryk BJ, Rousseau SM, Stump DC. Fibrinogen deposition and macrophage-associated fibrin formation in malignant and nonmalignant lymphoid tissue. J Lab Clin Med 1992; 119: 124-131
    PubMedGoogle Scholar
  • 5 Slichter SJ, Harker LA. Hemostasis in malignancy. Ann NY Acad Sci 1974; 230: 252-261
    CrossrefPubMedGoogle Scholar
  • 6 Peuscher FW, Cleton FJ, Armstrong L, Stoepman-van Dalen EA, van Mourik JA, van Aken WG. Significance of plasma fibrinopeptide A (fpA) in patients with malignancy. J Lab Clin Med 1980; 96: 5-14
    PubMedGoogle Scholar
  • 7 Dabrowska M, Kemona H, Prokopowicz J, Kretowska J, Kiluk S. Serum antithrombin III and alpha-2-antiplasmin concentrations in patients with Hodgkin’s disease in the course of chemotherapy. Neoplasma 1991; 38: 249-252
    PubMedGoogle Scholar
  • 8 Zurbom KH, Gram J, Glander K, Delbruck K, Pelzer H, Loffler H, Bruhn HD. Influence of cytostatic treatment on the coagulation system and fibrinolysis in patients with non-Hodgkin’s lymphomas and acute leukemias. Eur J Haematol 1991; 47: 55-59
    CrossrefPubMedGoogle Scholar
  • 9 Viero P, Cortelazzo S, Casarotto C, Barbui T, Colucci M, Semeraro N. Increased production of mononuclear cell procoagulant activity in Hodgkin’s disease. Eur J Cancer Clin Oncol 1983; 19: 1539-1543
    CrossrefPubMedGoogle Scholar
  • 10 Vassalli J-D, Dayer J-M, Wohlwend A, Belin D. Concomitant secretion of prourokinase and of plasminogen activator-specific inhibitor by cultured human monocytes-macrophages. J Exp Med 1984; 159: 1653-1668
    CrossrefPubMedGoogle Scholar
  • 11 Saksela O, Hovi T, Vaheri A. Urokinase-type plasminogen activator and its inhibitor secreted by cultured human monocytes-macrophages. J Cell Physiol 1985; 122: 125-132
    CrossrefPubMedGoogle Scholar
  • 12 Schwartz BS, Bradshaw JD. Regulation of plasminogen activator inhibitor mRNA levels in lipopolysaccharide-stimulated human monocytes. J Biol Chem 1992; 267: 7089-7094
    PubMedGoogle Scholar
  • 13 Scully MF. Plasminogen activator-dependent pericellular proteolysis. Br J Haematol 1991; 79: 537-533
    CrossrefPubMedGoogle Scholar
  • 14 Vassalli J-D, Sappino A-P, Belin D. The plasminogen activator/plasmin system. J Clin Invest 1991; 88: 1067-1072
    CrossrefPubMedGoogle Scholar
  • 15 Boyum A. Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol 1976; (Suppl. 05) 9-15
    PubMedGoogle Scholar
  • 16 Semeraro N, Biondi A, Lorenzet R, Locati D, Mantovani A, Donati MB. Direct induction of tissue factor synthesis by endotoxin in human macrophages from diverse anatomical sites. Immunology 1983; 50: 529-535
    PubMedGoogle Scholar
  • 17 Colucci M, Paramo JA, Collen D. Generation in plasma of a fast acting inhibitor of plasminogen activator in response to endotoxin. J Clin Invest 1985; 75: 818-824
    CrossrefPubMedGoogle Scholar
  • 18 Schwartz BS, Monroe MC, Levin EG. Increased release of plasminogen activator inhibitor type 2 accompanies the human mononuclear cell tissue factor response to lipopolysaccharide. Blood 1988; 71: 734-741
    PubMedGoogle Scholar
  • 19 Zuckerman SH, Surprenant YM. Induction of endothelial cell/macrophage procoagulant activity: synergistic stimulation by gamma-interferon and granulocyte-macrophage colony stimulating factor. Thromb Haemost 1989; 61: 178-182
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Conkling PR, Greenberg CS, Weinberg JB. Tumor necrosis factor induces tissue factor-like activity in human leukemia cell line U937 and peripheral blood monocytes. Blood 1988; 72: 128-133
    PubMedGoogle Scholar
  • 21 Clauss M, Gerlach M, Gerlach H, Brett J, Wang F, Familletti PC, Pan Y-CE, Olander JV, Connolly DT, Stem D. Vascular permeability factor: A tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 1990; 172: 1535-1545
    CrossrefPubMedGoogle Scholar
  • 22 Gyetko MR, Schollenberger SB, Sitrin RG. Urokinase expression in mononuclear phagocytes: cytokine-specific modulation by interferon-γ and tumor necrosis factor-α. J Leuk Biol 1992; 51: 256-263
    CrossrefPubMedGoogle Scholar
  • 23 Gyetko MR, Wilkinson CC, Sitrin RG. Monocyte urokinase expression: modulation by interleukins. J Leuk Biol 1993; 53: 598-601
    CrossrefPubMedGoogle Scholar
  • 24 Laiho M, Keski-Oja J. Growth factors in the regulation of pericellular proteolysis: A review. Cancer Res 1989; 49: 2533-2553
    PubMedGoogle Scholar
  • 25 Paramo JA, Colucci M, Collen D. Plasminogen activator inhibitor in the blood of patients with coronary artery disease. Br Med J 1985; 291: 573-574
    CrossrefPubMedGoogle Scholar
  • 26 Alessi MC, Juhan-Vague I, Declerck PJ, Anfosso F, Gueunoun E, Collen D. Correlations between t-PA and PAI-1 antigens and activity and t-PA/PAI complexes in plasma of control subjects and of patients with increased t-PA or PAI-1 levels. Thromb Res 1990; 60: 509-516
    CrossrefPubMedGoogle Scholar
  • 27 Brandtzaeg P, Joo GB, Brusletto B, Kierulf P. Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease. Thromb Res 1990; 57: 271-278
    CrossrefPubMedGoogle Scholar
  • 28 van Hinsbergh VWM, Bauer KA, Kooistra T, Kluft C, Dooijewaard G, Sherman ML, Nieuwenhuizen W. Progress of fibrinolysis during tumor necrosis factor infusions in humans. Concomitant increase in tissue-type plasminogen activator, plasminogen activator inhibitor type-1, and fibrin(ogen) degradation products. Blood 1990; 76: 2284-2289
    PubMedGoogle Scholar
  • 29 Colucci M, Paramo JA, Stassen JM, Collen D. Influence of the fast-acting inhibitor of plasminogen activator on in vivo thrombolysis induced by tissue-type plasminogen activator in rabbits. J Clin Invest 1986; 78: 138-144
    CrossrefPubMedGoogle Scholar