Activation of complement receptor 3 on human monocytes by cross-linking of very-late antigen-5 is mediated via protein tyrosine kinases.
Bordetella pertussis interacts with very-late antigen-5 (VLA-5) receptors on the human monocyte resulting in cross-linking of these receptors followed by activation of complement receptor 3 (CR3) and firm adhesion of B. pertussis to these monocytes. In the present study we investigated whether protein tyrosine kinases are involved in the activation of CR3 on monocytes, which was assessed by the binding of C3bi-coated erythrocytes (EC3bi). Pre-incubation of monocytes with tyrphostin-A47, a specific protein tyrosine kinase inhibitor, before adherence of the cells to an anti-VLA-5 monoclonal antibody-coated surface, or addition of tyrphostin-A47 within 10 min of the adherence to such surface, reduced the binding of EC3bi to monocytes significantly. Pre-incubation of monocytes with tyrphostin-A47 reduced the binding of B. pertussis to such monocytes as well. Inhibitors of protein kinase A and/or C had no effect on EC3bi binding to monocytes. Cross-linking of VLA-5 on monocytes resulted in tyrosine phosphorylation of several proteins. Together, these results indicate that protein tyrosine kinases are involved in the VLA-5-induced activation of CR3 on human monocytes.
van den Berg
B M
BM
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
van Furth
R
R
Hazenbos
W L
WL
D000911:Antibodies, Monoclonal; D001886:Bordetella pertussis / Q000276:immunology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003167:Complement Activation / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000276:immunology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017469:Receptors, Fibronectin / Q000276:immunology*; D019311:Staurosporine / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D047428:Protein Kinase Inhibitors; D017469:Receptors, Fibronectin; D020032:Tyrphostins; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine