Differential leukocyte recruitment from whole blood via endothelial adhesion molecules under shear conditions

被引:74
作者
Reinhardt, PH [1 ]
Kubes, P [1 ]
机构
[1] Univ Calgary, Fac Med, Dept Med Physiol, Immunol Res Grp, Calgary, AB T2N 4N1, Canada
关键词
D O I
10.1182/blood.V92.12.4691.424k18_4691_4699
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The objective of this study was to determine if vascular cell adhesion molecule (VCAM-1), E-selectin, and P-selectin could selectively recruit leukocyte subpopulations, and whether this was affected by shear force or adhesion molecule concentration. Cover slips coated with purified adhesion molecules were incorporated into laminar flow chambers. Whole human brood was perfused for 5 minutes over these cover slips at relative shear farces of 2 to 40 dynes/cm(2). Chasing the whole blood with buffer permitted visualization of leukocyte-substratum interactions. Leukocytes were observed to roll on and adhere to VCAM-1 at shears between 2 and 15 dynes/cm(2). As assessed by cover slip staining, the majority of these cells were lymphocytes, but eosinophils, monocytes, and, surprisingly, neutrophils were also recruited, events inhibitable by anti-alpha(4)-integrin antibody (HP1/2). Neutrophils were effectively recruited onto the selectins, with interactions occurring at shears as high as 30 and 40 dynes/cm(2) for E- and P-selectin respectively. Eosinophits had high affinity for P- but not E-selectin. Mononuclear cells did not have high affinity for either selectin, but interacted avidly with VCANI-1. Antibodies against P-selectin (G1) and E-selectin (ES-1) completely blocked interactions on these substrates. Reducing the concentration of adhesion molecules did not appreciably change recruitment patterns except for VCAM-1, where neutrophils were no longer recruited. The novel use of whole blood in flow chambers shows a partial selectivity of selectins and VCAM-1 for certain subpopulations of leukocytes under varying physiologic shear conditions. (C) 1998 by The American Society of Hematology.
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页码:4691 / 4699
页数:9
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