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J. Cell Biol.,
Volume 144, Number 5, March 8, 1999 1047-1056
1 Integrins by Chemoattractants Regulates
Neutrophil Migration through Fibrin


* Department of Physiology and Cellular Biophysics and Chemoattractants differ in their capacity to
stimulate neutrophils to adhere to and to migrate
through matrices containing fibrin. Formyl methionyl
leucyl phenylalanine (fMLP) stimulates neutrophils to
adhere closely to, but not to migrate into, fibrin gels.
Leukotriene B4 (LTB4) stimulates neutrophils to adhere loosely to and to migrate through fibrin gels. We
report that
Department of Pathology, Columbia University College of Physicians
and Surgeons, New York 10032;
Department of Medicine, Division of Rheumatology and Immunology, Medical University of
South Carolina, Charleston, South Carolina 29425-2229; § Department of Medicine, Beth Israel Hospital, New York 10004; and ¶ Athena Neurosciences, South San Francisco, California 94080
5
1 integrins regulate the different migratory behaviors on fibrin gels of neutrophils in response
to these chemoattractants. fMLP, but not LTB4, activated neutrophil
1 integrins, as measured by binding of
mAb 15/7 to an activation epitope on the
1 integrins.
Antibodies or peptides that block
5
1 integrins prevented fMLP-stimulated neutrophils from forming
zones of close apposition on fibrin and reversed fMLP's
inhibitory effect on neutrophil chemotaxis through fibrin. In contrast, neither peptides nor antibodies that
block
1 integrins affected the capacity of LTB4-stimulated neutrophils to form zones of loose apposition or
to migrate through fibrin gels. These results suggest that
chemoattractants generate at least two different messages that direct neutrophils, and perhaps other leukocytes, to accumulate at specific anatomic sites: a general
message that induces neutrophils to crawl and a specific
message that prepares neutrophils to stop when they
contact appropriate matrix proteins for activated
1 integrins.
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