从骨髓释放的多形核白细胞优先滞留于肺微血管中。

Polymorphonuclear leukocytes released from the bone marrow preferentially sequester in lung microvessels.

作者信息

van Eeden S F, Kitagawa Y, Klut M E, Lawrence E, Hogg J C

机构信息

University of British Columbia, Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.

出版信息

Microcirculation. 1997 Sep;4(3):369-80. doi: 10.3109/10739689709146801.

DOI:10.3109/10739689709146801

PMID:9329013

Abstract

OBJECTIVE

A hallmark of the systemic response to an inflammatory stimulus is the release of polymorphonuclear leukocytes (PMNs) from the bone marrow. This study was designed to measure the release of PMNs from the bone marrow and to determine their sequestration in the lung after an intravenous injection of either endotoxin (n = 5) or saline (n = 5).

METHODS AND RESULTS

The thymidine analogue 5'-bromo-2-deoxyuridine (BrdU) was used to pulse label dividing PMNs in the bone marrow of rabbits (n = 13), and immunohistochemistry and morphometry were used to detect the release of BrdU-labeled PMNs into the circulation and to determine their sequestration in the lung. Endotoxin treatment caused a drop in the circulating PMN counts (3.3 +/- 0.08 at baseline to 0.12 +/- 0.02 x 10(9)/L at 1 hour after endotoxin), which was followed by a neutrophilia at 8 hours (6.3 +/- 1.1 x 10(9)/L, P < 0.01), an increase in circulating band cells (0.12 +/- 0.01 at baseline to 2.18 +/- 0.4 x 1(9)/L at 8 hours, p < 0.001), and an increase in the percentage of BrdU-labeled PMNs (0.01% +/- 0.004% at baseline to 26.1% +/- 3.2% at 8 hours, p < 0.001). Endotoxemia caused an arteriovenous difference in BrdU-labeled PMNs across the lung (35.9% +/- 2.9% versus 26.1% +/- 3.1%, mixed venous versus arterial, p < 0.02). Morphometric studies showed that endotoxin caused sequestration of PMNs in the lung (2.2 +/- 0.4 versus 1.0 +/- 0.2 x 10(10), endotoxin versus saline, p < 0.03) with preferential retention of BrdU-labeled PMNs (0.79 +/- 0.21 versus 0.039 +/- 0.016 x 10(10), endotoxin versus saline, p < 0.05). The percentage of BrdU-labeled PMNs in the alveolocapillary walls was higher than in circulating blood (64.01% +/- 4.3% versus 26.1% +/- 3.2%, p < 0.01) in the endotoxin group. In vitro filtration of cells through 5-mm pore size filters showed that circulating BrdU-labeled PMNs, 8 hours after endotoxin, were preferentially retained in the filters (p < 0.01).

CONCLUSIONS

We conclude that endotoxemia stimulates the bone marrow to release mature and immature PMNs. Compared to PMNs released from the bone marrow during normal turnover, these PMNs are less deformable and preferentially sequester in the lung microvessels.

摘要

目的

对炎症刺激的全身反应的一个标志是骨髓中多形核白细胞（PMN）的释放。本研究旨在测量静脉注射内毒素（n = 5）或生理盐水（n = 5）后骨髓中PMN的释放，并确定其在肺中的滞留情况。

方法与结果

胸腺嘧啶核苷类似物5'-溴-2'-脱氧尿苷（BrdU）用于脉冲标记兔（n = 13）骨髓中正在分裂的PMN，采用免疫组织化学和形态计量学方法检测BrdU标记的PMN释放到循环中，并确定其在肺中的滞留情况。内毒素处理导致循环PMN计数下降（基线时为3.3±0.08，内毒素注射后1小时为0.12±0.02×10⁹/L），随后在8小时出现中性粒细胞增多（6.3±1.1×10⁹/L，P < 0.01），循环中杆状核细胞增加（基线时为0.12±0.01，8小时时为2.18±0.4×1⁹/L，p < 0.001），以及BrdU标记的PMN百分比增加（基线时为0.01%±0.004%，8小时时为26.1%±3.2%，p < 0.001）。内毒素血症导致肺内BrdU标记的PMN动静脉差异（混合静脉血与动脉血相比，分别为35.9%±2.9%和26.1%±3.1%，p < 0.02）。形态计量学研究表明，内毒素导致PMN在肺中滞留（内毒素组与生理盐水组分别为2.2±0.4和1.0±0.2×10¹⁰，p < 0.03），且BrdU标记的PMN优先滞留（内毒素组与生理盐水组分别为0.79±0.21和0.039±0.016×10¹⁰，p < 0.05）。内毒素组肺泡毛细血管壁中BrdU标记的PMN百分比高于循环血液中的百分比（分别为64.01%±4.3%和26.1%±3.2%，p < 0.01）。通过5毫米孔径滤器对细胞进行体外过滤显示，内毒素注射8小时后，循环中的BrdU标记的PMN优先滞留在滤器中（p < 0.01）。