Ontogenesis of Tissue Plasminogen Activator in the Human

Summary

The ontogenesis of tissue plasminogen activator in various tissues was studied in 10 embryos and 58 foetuses with a histochemical method.

The first appearance of activator activity was seen in a 4-weeks old embryo. At 8-9 weeks it was seen in the eye, meninges, heart, lungs, kidney and vena cava. In the foetal heart high activity was found in the coronary vessels, which can be regarded as the vasa vasorum of the heart. In the lungs a moderate activity increased at 24 weeks of age, when vascularisation increases more rapidly. Intense activity was seen in the highly vascularized corneoscleral junction of the eye later involved in the drainage of aqueous humor.

In the kidney the activity could be related to the vessels, while no activity was seen in the glomeruli, the collecting system or the pelvis. In the vessels the activator activity was fairly high. No activity was seen in any stage of development of the liver.

The plasminogen activator activity may be of importance for maintaining the foetomaternal circulation and micro-circulation in rapidly growing foetal organs. In the embryo the enzyme pattern is dominated by protein synthetizing enzymes. During foetal development the enzyme pattern changes owing to supervention of enzymes necessary for the function of the various organs. Plasminogen activator belongs to this latter group. The appearance of plasminogen activator activity may therefore be regarded mainly as a sign of functional maturity of the foetal organs.

• References

• 1 Albrechtsen O. K. The fibrinolytic activity of animal tissues. Acta physiol, scand 39: 284 1957;
• 2 Albrechtsen O. K. Fibrinolytic activity in the organism. Acta physiol, scand.. 47. Suppl. 165 1959
• 3 Ambrus G. M, Weintraub D. H, Niswander K. R, Ambrus J. L. Studies on hyaline membrane disease. II. The ontogeny of the fibrinolysin system. Pediatrics 35: 91 1965;
• 4 Astrup T. Fibrinolysis in the organism. Blood 09: 781 1956;
• 5 Astrup T. O, Albrechtsen K. Estimation of the plasminogen activator and the trypsin inhibitor in animal and human tissues. Scand. J. clin. Lab. Invest 09: 233 1957;
• 6 Astrup T, Müllertz S. The fibrin plate method for estimating fibrinolytic activity. Arch. Biochem 40: 346 1952;
• 7 Brakman P. Fibrinolysis. A standardized fibrin plate method and a fibrinolytic assay of plasminogen. Scheltema & Holkema; Amsterdam: 1967
• 8 Duke-Elder S. System of Opthalmology. Vol.Ill, Part 1, 186 Kimpton; London: 1963
• 9 Ekelund H, Hedner U, Àstedt B. Fbirinolysis in human foetuses. Acta paediat. Scand 59: 369 1970;
• 10 Fearnley G. R. Fibrinolysis. 56 Williams and Wilkins; Baltimore: 1965
• 11 Ladehoff A. a. Fibrinolytic tissue activity in the urogenital tract and the adrenal gland of human embryos and new-born. Acta paediat. scand 57: 500 1968;
• 12 Lieberman J. Clinical syndromes associated with deficient lung fibrinolytic activity. I. New concept of hyaline-membrane disease. New Engl. J. Med 260: 619 1959;
• 13 Lieberman J. Pulmonary plasminogen-activator activity in hyaline membrane disease. Pediat. Res 03: 11 1969;
• 14 McConnel D, Johnson I. G, Young I. Localization of plasminogen activator in kidney tissues. Lab. Invest 15: 980 1966;
• 15 Nilsson I. M, Hedner U, Isacson S, Larsson S. O, Pandolfi M. Fibrinolysis in renal disease. Symposium on the side effects of coagulation and fibrinolysis. Milano; 1969
• 16 Pandolfi M. Localization of fibrinolytic activity in the developing rat eye. Arch. Ophthal 78: 512 1967;
• 17 Pandolfi M. Studies on fibrinolysis in some tissues and in aqueous humor. Academic dissertation. Berlingska boktryckeriet. Lund: 1969
• 18 Pandolfi M, Kwaan H. G. Fibrinolysis in the anterior segment of the eye. Arch. Ophthal 77: 99 1967;
• 19 Pandolfi M, Nilsson I. M, Robertson B, Isacson S. Fibrinolytic activity of human veins. Lancet II: 127 1967;
• 20 Permin P. M. The fibrinolytic activator in animal tissue. Acta physiol, scand 21: 159 1950;
• 21 Richter D. Enzymatic activity during early development. Brit. med. Bull 17: 118 1961;
• 22 Todd A. S. Histological localization of fibrinolysin activator. J. Path. Bact 78: 281 1959;