IgE alone stimulates mast cell adhesion to fibronectin via pathways similar to those used by IgE + antigen but distinct from those used by Steel factor.
We recently demonstrated that immunoglobulin E (IgE), in the absence of cross-linking agents, activates signaling pathways in healthy murine bone marrow-derived mast cells (BMMCs) and that this activation enhances BMMC survival, at least in part, via secretion of autocrine-acting cytokines. We report herein that IgE alone also triggers the adhesion of both BMMCs and connective tissue mast cells (CTMCs) to the connective tissue component, fibronectin (FN). This adhesion occurs to the same extent as that triggered by optimal levels of Steel factor (SF) or IgE + antigen (IgE + Ag) and is mediated by an increased avidity of the integrin very late antigen 5 (VLA-5). Moreover, this IgE-induced adhesion, which is prolonged compared with that elicited by SF or IgE + Ag, requires phosphatidylinositol 3-kinase (PI3K), phospholipase C gamma (PLCgamma), and extracellular calcium but not extracellular-regulated kinase (Erk) or p38. Interestingly, we found, using the calcium channel blocker, 2-APB (2-aminoethoxydiphenyl borate) and Lyn-/- BMMCs that both IgE- and IgE + Ag-induced adhesion to FN require extracellular calcium entry, whereas SF does not. Furthermore, our data suggest that FN acts synergistically with IgE to prolong intracellular phosphorylation events and to enhance IgE-induced inflammatory cytokine production and BMMC survival.
Lam
Vivian
V
Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, Canada.
Kalesnikoff
Janet
J
Lee
Corinna W K
CW
Hernandez-Hansen
Valerie
V
Wilson
Bridget S
BS
Oliver
Janet M
JM
Krystal
Gerald
G
D016475:3T3 Cells; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism*; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D039081:Integrin alpha5beta1 / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051966:Phospholipase C gamma; D010766:Phosphorylation; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000276:immunology / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D019061:src-Family Kinases / Q000172:deficiency / Q000378:metabolism
D001896:Boron Compounds; D016207:Cytokines; D005353:Fibronectins; D039081:Integrin alpha5beta1; D019089:Stem Cell Factor; D007073:Immunoglobulin E; C109986:2-aminoethoxydiphenyl borate; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium