A novel beta 1 integrin-dependent mechanism of leukocyte adherence to apoptotic cells.
Adherence of leukocytes to cells undergoing apoptosis has been reported to be dependent on a variety of recognition pathways. These include alpha V beta 3 (CD51/CD61, vitronectin receptor), CD36 (thrombospondin receptor), macrophage class A scavenger receptor, phosphatidylserine translocated to the outer leaflet of apoptotic cell membranes, and CD14 (LPS-binding protein). We investigated the mechanism by which leukocytes adhere to apoptotic endothelial cells (EC). Peripheral blood mononuclear leukocytes and U937 monocytic cells adhered to human or bovine aortic EC induced to undergo apoptosis by withdrawal of growth factors, treatment with the promiscuous protein kinase inhibitor staurosporine, with the protein synthesis inhibitor and protein kinase activator anisomycin, or with the combination of cycloheximide and TNF-alpha. Expression of endothelial adherence molecules such as CD62E (E-selectin), CD54 (ICAM-1), and CD106 (VCAM-1) was not induced or increased by these treatments. A mAb to alpha V beta 3, exogenous thrombospondin, or blockade of phosphatidylserine by annexin V did not inhibit leukocyte adherence. Further, leukocyte binding to apoptotic EC was completely blocked by treatment of leukocytes but not EC with mAb to beta 1 integrin. These results define a novel pathway for the recognition of apoptotic cells.
Schwartz
B R
BR
Department of Medicine (Hematology), University of Washington School of Medicine, Seattle 98195, USA. brs@u.washington.edu
Karsan
A
A
Bombeli
T
T
Harlan
J M
JM
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010718:Phosphatidylserines / Q000502:physiology; D019030:Receptors, Vitronectin / Q000502:physiology; D019311:Staurosporine / Q000494:pharmacology; D020298:U937 Cells
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D019012:Integrin beta1; D010718:Phosphatidylserines; D019030:Receptors, Vitronectin; D019311:Staurosporine