J. Cell Biol., Volume 144, Number 5, March 8, 1999 1047-1056

Differential Regulation of ₁ 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 ₅₁ 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 ₅₁ 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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