Effects of human mast cell tryptase on the kinetics of blood clotting

Samoszuk, Michael; Corwin, Mark; Hazen, Stanley L.

doi:10.1016/s0049-3848(03)00150-6

Cited by 6 publications

(3 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PAR receptors may act as links between blood coagulation and inflammation, including mast cell activation [38]. However, a recent study has demonstrated that the anticoagulant activity of the human tryptase/heparin complex is attributable exclusively to the heparin associated with the tryptase and not to intrinsic activity of the tryptase [39]. As such, mast cells probably do play a role in inhibiting thrombosis, but by mechanisms independent of the intrinsic activity of tryptase.…”

Section: Protease Activated Receptorsmentioning

confidence: 99%

Mast cell tryptase: a review of its physiology and clinical significance

Payne¹,

2004

View full text Add to dashboard Cite

SummaryMast cells, which are granulocytes found in peripheral tissue, play a central role in inflammatory and immediate allergic reactions. b-Tryptase is a neutral serine protease and is the most abundant mediator stored in mast cell granules. The release of b-tryptase from the secretory granules is a characteristic feature of mast cell degranulation. While its biological function has not been fully clarified, mast cell b-tryptase has an important role in inflammation and serves as a marker of mast cell activation. b-Tryptase activates the protease activated receptor type 2. It is involved in airway homeostasis, vascular relaxation and contraction, gastrointestinal smooth muscle activity and intestinal transport, and coagulation. Serum mast cell b-tryptase concentration is increased in anaphylaxis and in other allergic conditions. It is increased in systemic mastocytosis and other haematological conditions. Serum b-tryptase measurements can be used to distinguish mast cell-dependent reactions from other systemic disturbances such as cardiogenic shock, which can present with similar clinical manifestations. Increased b-tryptase levels are highly suggestive of an immunologically mediated reaction but may also occur following direct mast cell activation. Patients with increased mast cell b-tryptase levels must be investigated for an allergic cause. However, patients without increased mast cell tryptase levels should be investigated if the clinical picture suggests severe anaphylaxis.

show abstract

Section: Protease Activated Receptorsmentioning

confidence: 99%

Mast cell tryptase: a review of its physiology and clinical significance

Payne¹,

2004

View full text Add to dashboard Cite

show abstract

“…Mast cell tryptase has potent fibrinogenolytic activity in vitro ,5 and there has been speculation that this activity may account for the strong anticoagulant properties of tryptase 9. We have demonstrated recently, however, that the anticoagulant activity of human mast cell tryptase in human blood is probably attributable to the mast cell heparin that is associated tightly with the tryptase in mast cell granules 10. Although the intrinsic enzymatic activity of mast cell tryptase probably does not account for its powerful anticoagulant activity, the enzyme is nonetheless an excellent and highly specific marker of mast cell degranulation in tissues and in blood 11.…”

mentioning

confidence: 92%

Mast cell inhibitor cromolyn increases blood clotting and hypoxia in murine breast cancer

Samoszuk

Corwin

2003

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Human breast cancer is extensively infiltrated by mast cells that contain powerful anticoagulants such as heparin, tryptase and chymase. To determine if human breast cancer is associated with mast cell activation, we measured the levels of mast cell tryptase (an indicator of mast cell activation) in the blood of 20 women with varying stages of breast cancer. The mean level of tryptase in women with breast cancer (10.3 ؎ 4.2 g/L) was significantly higher than in 50 normal healthy women without breast cancer (3.0 ؎ 2.5 g/L, p < 0.05 by two-tailed t-test). To explore the role of mast cells in breast cancer in more detail, we then carried out experiments that were aimed at determining if an inhibitor of mast cell function, sodium cromolyn, could increase blood clotting and hypoxia within subcutaneous implants of the 4T1 mammary adenocarcinoma cell line in mice. We treated tumor-bearing mice with 5 consecutive daily doses of sodium cromolyn (10 mg/kg, i.p.). An average of 30% of the periphery of the tumors from the 5 drug-treated mice contained large lakes of clotted blood that were not evident in any of the tumors from the control (untreated) mice. By computerized image analysis of tumors immunostained for a hypoxia marker (pimonidazole), the tumors from the treated mice had significantly more hypoxia (35 ؎12 % hypoxic regions, n ‫؍‬ 5) than the tumors from untreated (control) mice (16 ؎ 7%, n ‫؍‬ 5). We conclude that sodium cromolyn enhanced peri-tumoral blood clotting and intratumoral hypoxia. These results suggest that mast cells may play an important role in regulating blood clotting and hypoxia within breast cancer.

show abstract

“…[20] Further studies showed that inhibition of b-tryptase by the peptide ligands examined is reversible (enzyme activity could be restored by dialysis with buffer). Another variant of tryptase, heparin-free rhLung b-tryptase, [21] is also inhibited by these ligands (e.g., (KKFG) 4 has a K i value of 323 nm). Hence, heparin (a polyanion and a possible binding partner for cationic molecules) cannot be the target of our inhibitors.…”

mentioning

confidence: 99%