We have examined the capacity of four different chemoattractants/cytokines to promote directed migration of polymorphonuclear leukocytes (PMN) through three-dimensional gels composed of extracellular matrix proteins. About 20% of PMN migrated through fibrin gels and plasma clots in response to a gradient of interleukin 8 (IL-8) or leukotriene B4 (LTB4). In contrast, < 0.3% of PMN migrated through fibrin gels in response to a gradient of tumor necrosis factor alpha (TNF) or formyl-methionyl-leucyl-phenylalanine (FMLP). All four chemoattractants stimulated PMN to migrate through gels composed of collagen IV or of basement membrane proteins (Matrigel), or through filters to which fibronectin or fibrinogen had been adsorbed. PMN stimulated with TNF or FMLP adhered and formed zones of close apposition to fibrin, as measured by the exclusion of a 10-kD rhodamine-polyethylene glycol probe from the contact zones between PMN and the underlying fibrin gel. By this measure, IL-8- or LTB4-treated PMN adhered loosely to fibrin, since 10 kD rhodamine-polyethylene glycol permeated into the contact zones between these cells and the underlying fibrin gel. PMN stimulated with FMLP and IL-8, or FMLP and LTB4, exhibited very little migration through fibrin gels, and three times as many of these cells excluded 10 kD rhodamine-polyethylene glycol from their zones of contact with fibrin as PMN stimulated with IL-8 or LTB4 alone. These results show that PMN chemotaxis is regulated by both the nature of the chemoattractant and the composition of the extracellular matrix; they suggest that certain combinations of chemoattractants and matrix proteins may limit leukocyte movements and promote their localization in specific tissues in vivo.
Article|
May 01 1995
Fibrin regulates neutrophil migration in response to interleukin 8, leukotriene B4, tumor necrosis factor, and formyl-methionyl-leucyl-phenylalanine.
J D Loike,
J D Loike
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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J el Khoury,
J el Khoury
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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L Cao,
L Cao
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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C P Richards,
C P Richards
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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H Rascoff,
H Rascoff
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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J T Mandeville,
J T Mandeville
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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F R Maxfield,
F R Maxfield
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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S C Silverstein
S C Silverstein
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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J D Loike
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
J el Khoury
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
L Cao
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
C P Richards
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
H Rascoff
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
J T Mandeville
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
F R Maxfield
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
S C Silverstein
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 181 (5): 1763–1772.
Citation
J D Loike, J el Khoury, L Cao, C P Richards, H Rascoff, J T Mandeville, F R Maxfield, S C Silverstein; Fibrin regulates neutrophil migration in response to interleukin 8, leukotriene B4, tumor necrosis factor, and formyl-methionyl-leucyl-phenylalanine.. J Exp Med 1 May 1995; 181 (5): 1763–1772. doi: https://doi.org/10.1084/jem.181.5.1763
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