fibrinopeptide-a and Pleural-Effusion

The ability of various peptides cleaved by plasmin from human fibrinogen and fibronectin or fibrinogen- and fibronectin- related synthetic peptides to induce histamine release from mast cells and collagenase and elastase from PMN-leukocytes was examined. Low molecular weight fibrinogen degradation products showed dose dependent secretion of collagenase. These peptides (mol. wt. 1.4 kD) at the concentration of 10(-5) M released about 47% of collagenase and 13% of elastase. Synthetic fibrinopeptides A and B had a similar strong collagenase releasing potency and also released histamine from mast cells. Peptides from plasmin digestion of fibronectin containing cell attachment site with sequence Arg-Gly-Asp-Ser and also synthetic peptide reproducing this amino-acid sequence at the concentration of 1000 micrograms/ml released about 50% of collagenase and 55% of elastase from PMN-leukocytes. Moreover peptides containing cell attachment and gelatin binding site induced histamine release from mast cells. The association of fibrinogen and fibronectin degradation with activation of mast cells may motivate the treatment with antihistaminic drugs of all pathological conditions where the intensive protein degradation takes place.

Topics: Animals; Ascitic Fluid; Cell Degranulation; Collagenases; Fibrinopeptide A; Fibrinopeptide B; Fibronectins; Histamine Release; In Vitro Techniques; Male; Mast Cells; Models, Biological; Neutrophils; Pancreatic Elastase; Pleural Effusion; Rats; Rats, Wistar

Pleural fluid from an early, active phase of BCG-induced pleurisy was compared with fluid from late, healing phase, characterized by fibrinous adhesions. Exudates were tested for proteolytic activity on chromogenic peptide substrates designed for plasmin, tissue plasminogen activator, factor Xa, thrombin and plasma kallikrein. Considerable activity of active-phase pleural fluid was found on all of these substrates, and significantly lower values in the healing phase. Most exudates from both stages had very low fibrinogen concentration. Fibrinopeptide A, fibrinolytic products and antiplasmin were found in all exudates. Little or no fibrinolytic effect of pleural fluid was demonstrable on plasminogen free fibrin plates, despite the high activities on the low molecular weight substrates. Occurrence of alpha 2-macroglobulin-enzyme complexes is suggested as an explanation. The experimental results indicate that protease of the fibrinolytic and coagulation systems are active in the chronic inflammation of pleurisy, with higher levels of activity in active pleurisy phase.

Topics: alpha-2-Antiplasmin; Animals; Blood Coagulation; Factor X; Factor Xa; Female; Fibrinogen; Fibrinolysin; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Guinea Pigs; Kallikreins; Male; Mycobacterium bovis; Plasminogen Activators; Pleural Effusion; Thrombin; Tuberculosis, Pleural

Fibrinogen, fibrin(ogen) degradation products (FDP) and fibrinopeptide A (FPA) were analysed in pleural fluids from 20 consecutive patients with major effusions of various aetiology. FPA is a short-lived polypeptide which is split off from fibrinogen, whereafter fibrin is formed. FDP are formed through lysis of fibrin or fibrinogen. In 18 patients no fibrinogen could be detected in pleural fluid, whereas two (both having malignant tumours) had detectable but low concentrations. High FPA concentrations, interpreted as reflecting very recent fibrin formation, were found in all pleural fluids except for one case of empyema and one transudate. Plasma concentrations were low in most cases. The same pattern was found with regard to FDP, i.e. exudates showed high concentrations, whereas plasma concentrations were low. The only patient with a transudate showed absence of fibrinogen and low concentrations of FDP and FPA. We interpret our findings as indicative of a high rate of fibrin formation and degradation in pleural exudates and have not found any differences between various types of pleural exudates. Consequently, the findings may illustrate the close association between the coagulation system and inflammatory reactions which may be common to most pleural diseases.

Topics: Adult; Aged; Bronchial Neoplasms; Empyema; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Pleural Effusion; Pleural Neoplasms; Pleurisy

In 13 patients with effusions of varying etiology, considerably higher fibrinopeptide A (FPA) immunoreactivity were found in the effusions than in the corresponding plasmas. After instillation of heparin into the effusion the FPA concentration diminished significantly but very slowly. The difference in concentration between plasma and effusion therefore represents a relative FPA accumulation in the effusion. In view of its extremely short half-life in plasma, the FPA produced in the effusions is thought not to contribute to the increased plasma FPA levels. In addition, injection of amounts of FPA into the effusion such as to produce an acute increase of the local FPA level did not lead to a significant change in the FPA level in plasma.

Topics: Breast Neoplasms; Bronchial Neoplasms; Fatty Liver; Female; Fibrinogen; Fibrinopeptide A; Half-Life; Humans; Liver Cirrhosis; Lymphoma, Non-Hodgkin; Pleural Effusion