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© The Rockefeller University Press, 0021-9525/1999//1047 $5.00
The Journal of Cell Biology, Volume 144, Number 5, , 1999 1047-1056

Differential Regulation of β₁ Integrins by Chemoattractants Regulates Neutrophil Migration through Fibrin

John D. Loike^*, Long Cao^*, Sadna Budhu^*, Eugene E. Marcantonio, Joseph El Khoury, Stanley Hoffman^||, Ted A. Yednock^¶, and Samuel C. Silverstein^*

^* Department of Physiology and Cellular Biophysics and 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

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 ₅β₁ integrins regulate the different migratory behaviors on fibrin gels of neutrophils in response to these chemoattractants. fMLP, but not LTB4, activated neutrophil β₁ integrins, as measured by binding of mAb 15/7 to an activation epitope on the β₁ integrins. Antibodies or peptides that block ₅β₁ 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 β₁ 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 β₁ integrins.

Key Words: chemotaxis • neutrophils • integrins • fibrin • chemoattractants

Abbreviations used in this paper: C3bi, cleaved b fragment of the 3rd complement component; C5a, a fragment of the cleaved 5th complement component; fMLP, formyl methionyl leucyl phenylalanine; HSA, human serum albumin; IL-8, interleukin 8; LTB4, leukotriene B4; PMN, polymorphonuclear leukocytes; Rh-PEG, rhodamine-conjugated polyethylene glycol.

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