Dynamics of platelet mobilisation into lungs in response to 5-hydroxytryptamine (serotonin) in mice

Zhiqian Yu; Mami Ohba; Masanori Nakamura; Takashi Sasano; Masao Ono; Shunji Sugawara; Yasuo Endo

doi:10.1160/TH08-06-0406

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(06): 1251-1258
DOI: 10.1160/TH08-06-0406

Platelets and Blood Cells

Schattauer GmbH

Dynamics of platelet mobilisation into lungs in response to 5-hydroxytryptamine (serotonin) in mice

Authors

Zhiqian Yu

¹Department of Oral Diagnosis, Graduate School of Dentistry, Tohoku University, Sendai, Japan

²Department of Oral Molecular Regulation, Graduate School of Dentistry, Tohoku University, Sendai, Japan
Mami Ohba

¹Department of Oral Diagnosis, Graduate School of Dentistry, Tohoku University, Sendai, Japan

²Department of Oral Molecular Regulation, Graduate School of Dentistry, Tohoku University, Sendai, Japan
Masanori Nakamura

³Department of Anatomy, School of Dentistry, Showa University, Tokyo, Japan
Takashi Sasano

¹Department of Oral Diagnosis, Graduate School of Dentistry, Tohoku University, Sendai, Japan
Masao Ono

⁴Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai, Japan
Shunji Sugawara

²Department of Oral Molecular Regulation, Graduate School of Dentistry, Tohoku University, Sendai, Japan
Yasuo Endo

²Department of Oral Molecular Regulation, Graduate School of Dentistry, Tohoku University, Sendai, Japan

Abstract

Summary

In experimental animals, the lung rapidly removes intravenously injected 5-hydroxytryptamine (5HT), but the mechanism underlying this pulmonary 5HT removal (P-5HT-R) and the responsible cells remains unclear. 5HT reportedly induces rapid pulmonary platelet accumulation (P-PLT-A). Here, we examined the relationship between P-5HT-R and P-PLT-A in mice by comparing the platelet count in the blood with the endogenous 5HT in the tissues (a marker for platelets because the 5HT is largely contained within platelets). 5HT levels in murine blood and tissues were also examined after intravenous injection of 5HT. The data revealed that: (i) 5HT injection (at ≥ 0.04 μmol/kg) induced a transient P-PLT-A (occurring within 6 seconds), (ii) platelets rapidly took up injected 5HT, (iii) the P-5HT-R was saturated following injection of 5HT at 1 μmol/kg, (iv) ketanserin (5HT₂-receptor antagonist) strongly inhibited P-PLT-A, (v) under fluoxetine (5HT-uptake inhibitor), 5HT levels at 6 seconds after 5HT injection were markedly higher in blood, but significantly lower in lung (versus fluoxetine-untreated mice), (vi) P-5HT-R was barely detectable in mutant mice with platelets lacking dense bodies, and was much reduced in platelet-depleted mice, (vii) 5HT injected intravenously at 10 μmol/kg had a half-life in the lung of < 20 seconds, and (viii) unlike 5HT, injected histamine was largely excreted by the kidney. These results demonstrate that platelets rapidly translocate into the lung upon stimulation of 5HT2 receptors, take up 5HT (and possibly swiftly metabolise it), and then return to the circulation. Hence, pulmonary platelet accumulation plays an important role in pulmonary 5HT removal in mice.

Keywords

Platelet - lung - 5-hydroxytryptamine - animal model

Full Text

References

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