The role of platelets and leukocytes in endogenous fibrinolysis.

The impact of intravascular aggregation of circulating platelets and white blood cells on the plasma activity of t-PA and PAI-1 was measured. In vivo platelet and white blood cell aggregation was induced by platelet and white blood cell agonists, the effect being monitored by the Technicon autocounter. Plasma activity of t-PA and PAI-1 was measured using the amidolytic technique. Three potent platelet agonists (collagen, ADP and thrombin) each caused significant and non-selective decreases in the number of circulating platelets and white blood cells at the same intravenous doses. Dose-response curves were superimposable in each case, suggesting a close functional and/or physical relationship between circulating platelets and white blood cells. This conclusion was supported by inhibition of collagen-induced white blood cell aggregation by indomethacin, at identical doses to those which affect platelet function. Histopathology of sectioned lung tissue, following intravenous administration of collagen, showed the accumulation of white blood cells in the micro-circulation. In contrast, two potent white blood cell agonists (fMLP and PAF) caused dose-dependent, selective and substantial decreases in circulating white blood cell counts, with relatively little (fMLP) and no (PAF) effect on circulating platelet count. These data suggest a different mechanism for white blood cell activation in the rat which does not also involve circulating platelets. There were no dose-related changes in plasma activity of t-PA and PAI-1 following acute administration of collagen, ADP or thrombin. In contrast, both fMLP and PAF induced a dose-related increase in t-PA activity. Where any change in PAI-1 activity was observed, this was a decrease, demonstrating that in vivo platelet aggregation does not generally lead to an increased PAI-1 activity in the rat. Total fibrinolytic capacity was measured by ECLT technique. Shortened lysis times correlated with increased t-PA activity at the high dose of PAF, and unchanged ECLT with lack of variation in t-PA and PAI-1 activity following collagen. The technique of SDS-PAGE with zymography confirmed the presence of t-PA and PAI-1 antigen in rat plasma. Moreover, this approach was subsequently used to show the presence of PAI-1 in rat platelets, and to obtain semi-quantitative estimates of its concentration.

Grantor dc:publisher.institution

Robert Gordon University

Year dc:date.issued

1992

Author dc:creator

• Fundafunda, Bonface C.

Advisor dc:contributor.advisor

• K. Kendle and D.P. Tuffin

• Platelets
• Leukocytes
• Endogenus fibrinolsis
• White blood cells
• Technicon autocounter
• Amidolytic technique
• Indomethacin
• Collagen
• Histopathology
• Lung tissue
• In vivo
• Zymography

Language dc:language

en

Identifier

oai:rgu-repository.worktribe.com:2807389
https://doi.org/10.48526/rgu-wt-2807389

OAI identifier oai:identifier

oai:rgu-repository.worktribe.com:2807389