| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
2 Integrin Affinity and Valency in Neutrophils, but Are Required for 2 Integrin-Mediated Outside-In Signaling Involved in Sustained Adhesion1
* Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy; and
Department of Laboratory Medicine, University of California, San Francisco, CA 94143
Neutrophil 
2 integrins are activated by inside-out signaling regulating integrin affinity and valency; following ligand binding, 2 integrins trigger outside-in signals regulating cell functions. Addressing inside-out and outside-in signaling in hck–/–fgr–/– neutrophils, we found that Hck and Fgr do not regulate chemoattractant-induced activation of 2 integrin affinity. In fact, 2 integrin-mediated rapid adhesion, in static condition assays, and neutrophil adhesion to glass capillary tubes cocoated with ICAM-1, P-selectin, and a chemoattractant, under flow, were unaffected in hck–/–fgr–/– neutrophils. Additionally, examination of integrin affinity by soluble ICAM-1 binding assays and of 2 integrin clustering on the cell surface, showed that integrin activation did not require Hck and Fgr expression. However, after binding, hck–/–fgr–/– neutrophil spreading over 2 integrin ligands was reduced and they rapidly detached from the adhesive surface. Whether alterations in outside-in signaling affect sustained adhesion to the vascular endothelium in vivo was addressed by examining neutrophil adhesiveness to inflamed muscle venules. Intravital microscopy analysis allowed us to conclude that Hck and Fgr regulate neither the number of rolling cells nor rolling velocity in neutrophils. However, arrest of hck–/–fgr–/– neutrophils to >60 µm in diameter venules was reduced. Thus, Hck and Fgr play no role in chemoattractant-induced inside-out 2 integrin activation but regulate outside-in signaling-dependent sustained adhesion.
This article has been cited by other articles:
|
|
 |
|
  R. Paul, B. Obermaier, J. Van Ziffle, B. Angele, H.-W. Pfister, C. A. Lowell, and U. Koedel Myeloid Src kinases regulate phagocytosis and oxidative burst in pneumococcal meningitis by activating NADPH oxidase J. Leukoc. Biol., October 1, 2008; 84(4): 1141 - 1150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Boylan, C. Gao, V. Rathore, J. C. Gill, D. K. Newman, and P. J. Newman Identification of Fc{gamma}RIIa as the ITAM-bearing receptor mediating {alpha}IIb{beta}3 outside-in integrin signaling in human platelets Blood, October 1, 2008; 112(7): 2780 - 2786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zarbock, T. L. Deem, T. L. Burcin, and K. Ley G{alpha}i2 is required for chemokine-induced neutrophil arrest Blood, November 15, 2007; 110(10): 3773 - 3779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Fumagalli, H. Zhang, A. Baruzzi, C. A. Lowell, and G. Berton The Src Family Kinases Hck and Fgr Regulate Neutrophil Responses to N-Formyl-Methionyl-Leucyl-Phenylalanine J. Immunol., March 15, 2007; 178(6): 3874 - 3885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Evangelista, Z. Pamuklar, A. Piccoli, S. Manarini, G. Dell'Elba, R. Pecce, N. Martelli, L. Federico, M. Rojas, G. Berton, et al. Src family kinases mediate neutrophil adhesion to adherent platelets Blood, March 15, 2007; 109(6): 2461 - 2469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. F. Smith, T. L. Deem, A. C. Bruce, J. Reutershan, D. Wu, and K. Ley Leukocyte phosphoinositide-3 kinase {gamma} is required for chemokine-induced, sustained adhesion under flow in vivo J. Leukoc. Biol., December 1, 2006; 80(6): 1491 - 1499. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
