Beta1 integrin activation on human neutrophils promotes beta2   integrin-mediated adhesion to fibronectin.
Although the importance of beta1 integrin-mediated binding to adhesion molecules and extracellular matrix (ECM) molecules is well established for most types of leukocytes, the expression patterns and functional importance of beta1 integrins on neutrophils have remained controversial. Using flow cytometry, we found that human neutrophils express the alpha4, alpha5, alpha9 and beta1 integrin subunits. To examine whether the integrins VLA-4 (alpha4/beta1) and VLA-5 (alpha5/beta1) have a functional role on neutrophils, we studied adhesion to their ligand fibronectin. Treatment of neutrophils with antibody 8A2, which specifically binds and activates beta1 integrins, resulted in increased binding to fibronectin. However, addition of blocking mAb revealed that 8A2-induced adhesion did not depend on beta1 integrins, but on the beta2 integrin CD11b/CD18. Similarly, activation of beta1 integrins by 8A2 resulted in CD11b-dependent binding of neutrophils to fibrinogen. 8A2 treatment increased expression of an activation epitope of CD11b/CD18, which depended on phosphoinositide 3-OH kinase activity and an adequate concentration of intracellular free Ca2+. These data suggest that engagement of beta1 integrins on neutrophils results in a cross-talk signal that leads to activation of the beta2 integrin CD11b/CD18, followed by CD11b-mediated adhesion. As transmigrated neutrophils are surrounded by both beta1 and beta2 ligands in the ECM, this integrin cross-talk could play a role in modifying migration and cellular activation in inflamed tissues.
CLB, Sanquin Blood Supply Foundation and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J M
JM
van den Berg
F P
FP
Mul
E
E
Schippers
J J
JJ
Weening
D
D
Roos
T W
TW
Kuijpers
D000730:Androstadienes / Q000494:pharmacology; D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*; D017469:Receptors, Fibronectin / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D018821:CD18 Antigens; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D016177:Macrophage-1 Antigen; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000077191:Wortmannin