(Stroke. 2001;32:1932.)
© 2001 American Heart Association, Inc.
Letters to the Editor |
4 Integrin Inhibit the Function of Lymphocytes and Monocytes?
Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
To the Editor:
We read with great interest the article by Becker and colleagues1 in the January 2001 issue of Stroke, in which the authors sought to assess the contribution of lymphocytes and monocytes to ischemic brain injury. They found that the administration of TA-2, an antibody against
4 integrin, reduced infarct size and improved neurological outcome when given 2 hours after a stroke. They also observed a peripheral leukocytosis with lymphocyte/monocyte predominance. Because the
4 integrin is thought to be found predominantly on lymphocytes and monocytes rather than neutrophils, they concluded that blockade of the
4 integrin reduced ischemic brain injury by antagonizing the functions of lymphocytes and monocytes. Although TA-2 binding of monocytes has been reported,2 Becker and colleagues neglected to present direct evidence showing that TA-2 administration ultimately blocked lymphocyte/monocyte infiltration and accumulation in the ischemic brain.
We would like to bring to the authors attention our study3,4 on the role of
4 integrin in the cell adhesion process. This study revealed that the alternately spliced connecting segment domain (CS-1) of the extracellular matrix protein fibronectin, which interacts with
4 integrin and inhibits monocyte adhesion, inhibits neutrophil accumulation in ischemic brain and reduces infarct size.3 The reduction of neutrophil accumulation by
4 integrin-binding CS-1 peptide seems inconsistent, because neutrophils are devoid of cell surface
4 integrins. Neutrophils can be detected as early as 30 minutes after and peak at 24 hours after ischemia in rat brain.5 In contrast, monocytes are first detected in ischemic tissue 4 to 6 hours
Department of Neurology
Division of Hematology, Department of Medicine
Department of Surgery, University of Washington School of Medicine, Harborview Medical Center, Seattle, Washington
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