Integrin alpha v beta 3 differentially regulates adhesive and phagocytic functions of the fibronectin receptor alpha 5 beta 1.
The plasma protein fibronectin is an important opsonin in wound repair and host defense. To better understand the process of fibronectin-mediated phagocytosis, we have transfected K562 cells, which endogenously express alpha 5 beta 1, with alpha v beta 3. In these transfectants, antibodies to alpha v beta 3 block phagocytosis of fibronectin-opsonized beads completely, even though half the ingestion occurs through endogenous alpha 5 beta 1 receptors. alpha 5 beta 1-mediated adhesion to fibronectin-coated surfaces is unaffected by alpha v beta 3 ligation. Neither alpha v beta 5 nor alpha M beta 2 ligation affects alpha 5 beta 1 phagocytic function in transfectants expressing these receptors. Pharmacologic data suggest that alpha v beta 3 ligation suppresses the phagocytic competence of high affinity alpha 5 beta 1 receptors through a signal transduction pathway, perhaps involving protein kinase C. In addition to its significance for phagocytosis, alpha v beta 3 regulation of alpha 5 beta 1 function may be significant for its roles in cell migration, metastasis, and angiogenesis.
Blystone
S D
SD
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Graham
I L
IL
Lindberg
F P
FP
Brown
E J
EJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D016227:Benzoquinones; D002448:Cell Adhesion; D002460:Cell Line; D003001:Cloning, Molecular; D005353:Fibronectins / Q000302:isolation & purification / Q000378:metabolism; D005434:Flow Cytometry; D019833:Genistein; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D047029:Lactams, Macrocyclic; D004915:Leukemia, Erythroblastic, Acute; D009281:Naphthalenes; D010587:Phagocytosis / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D016024:Receptors, Cytoadhesin / Q000096:biosynthesis / Q000502:physiology*; D017469:Receptors, Fibronectin / Q000096:biosynthesis / Q000502:physiology*; D019030:Receptors, Vitronectin; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D016227:Benzoquinones; D005353:Fibronectins; D016023:Integrins; D007529:Isoflavones; D007546:Isoquinolines; D047029:Lactams, Macrocyclic; D009281:Naphthalenes; D010879:Piperazines; D011083:Polycyclic Compounds; D047428:Protein Kinase Inhibitors; D011809:Quinones; D016024:Receptors, Cytoadhesin; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D017828:Rifabutin; C020754:herbimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; C058819:calphostin C