Inhibition of Platelet Aggregation by Mononuclear Leukocytes.
- Author:
Eun Ah CHANG
1
;
Young Joo CHA
Author Information
1. Department of Clinical Pathology, College of Medicine, Chung-Ang University, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Collagen;
Platelet Aggregation;
Mononuclear Leukocytes
- MeSH:
Blood Cells;
Blood Platelets*;
Collagen;
Endothelium, Vascular;
Epoprostenol;
Gravitation;
Humans;
Indomethacin;
Leukocytes, Mononuclear*;
Models, Theoretical;
Neutrophils;
Nitric Oxide;
Nitric Oxide Synthase;
omega-N-Methylarginine;
Platelet Aggregation*;
Platelet Count;
Platelet-Rich Plasma;
Prostaglandins
- From:Korean Journal of Hematology
1998;33(3):398-405
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Although normal vascular endothelium prevents adhesion and aggregation of platelets by the release of nitric oxide (NO) and prostacyclin, circulating blood cells, such as polymorphonuclear leukocytes (PMNs) and mononuclear leukocytes (ML) may be considered to be also important in modulating platelet aggregation. Recently, nitric oxide synthase (NOS) activity was found in PMNs and ML, so these cells can also release NO to inhibit platelet aggregation. We studied platelet-ML interactions using an experimental model in which isolated ML were placed in the aggregometer in contact with human platelets, stimulated by collagen. METHODS: Platelet count in platelet-rich plasma (PRP) was adjusted to approximately 300x109/L. ML were separated using Ficoll-Hypaque (specific gravity 1.077) and finally resuspended at 1, 3 and 5x109/L, in Tyrode albumin buffer (TAB), respectively. Platelet aggregation was measured with Chrono-Log Aggregometer (USA) after adding variable numbers of the ML, stimulating with 2.5, 5 and 10 microgram/mL of collagen. Mechanisms of ML to inhibit the platelet aggregation were evaluated after incubating the ML with 10 micrometer indomethacin and 300 micrometer NG-monomethyl-L-arginine (L-NMMA). RESULTS: Non-stimulated ML (3x109/L) inhibited (43.2 +/- 19.6 versus TAB control 69.2 +/- 10.7% transmission) the platelet aggregation induced by 2.5 microgram/mL of collagen. The inhibition was not attenuated by increasing the concentration of collagen from 5.0 microgram/ mL (50.1 +/- 18.0% versus TAB control 75.5 +/- 13.1%, P<0.001) to 10 microgram/mL (62.9 +/- 17.3% versus TAB contol 82.3 +/- 12.6%, P<0.01). In addition, it was dependent on the number of ML and incubation time. While preincubation of the ML with indomethcin did not affect the antiaggregating capacity of the ML (63.4 +/- 11.1 versus TAB control 73.3 +/- 7.3%), preincubation of the ML with L-NMMA slightly inhibit the antiaggregating capacity of the ML (86.6 +/- 6.8 versus TAB control 73.3 +/- 7.3%). CONCLUSION: These findings suggest that blood ML inhibited the collagen-induced platelet aggregation, of which mechanism appears to be only partly dependent on NO and to be independent on prostaglandins. Release of other substances affecting platelet aggregation from ML requires to be clarified. Using our experimental model, it has been demonstrated that cell-cell contact may facilitate the exchange of a wide array of mediators between platelets and ML which may influence the cellular responses. This experimental model thus allows to study interactions between platelets and ML.
