Polymerization of actin does not regulate desensitization in human basophils.
Previous studies have suggested that maintenance of IgE-mediated signaling results from regulation of the activity of signaling complexes by actin polymerization. This process is also hypothesized to be related to desensitization of basophils and mast cells. Recent studies demonstrated that any signaling process dependent on syk or PI-3K activity cannot be a mechanism of desensitization, and in this context, syk and PI-3K inhibitors were found to inhibit actin polymerization. Inhibitors of actin polymerization were tested for their effect on desensitization of human peripheral blood basophils. Latrunculin A, in particular, removed all resting and stimulated f-actin but did not inhibit desensitization. Cytochalasin D and latrunculin A also did not reverse the loss of syk phosphorylation that accompanies desensitization. These results demonstrate that desensitization mechanisms are not dependent on actin polymerization. In this context, it was also shown that progressive immobilization of Fc epsilon RI during aggregation was sensitive to syk or actin polymerization inhibition. Therefore, desensitization is also not dependent on receptor immobilization. These studies demonstrate that desensitization is not the result of two signaling pathways once considered relevant to down-regulation of IgE-mediated signaling.
MacGlashan
Donald
D
Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. dmacglas@jhmi.edu
Vilariño
Natalia
N
D000199:Actins / Q000378:metabolism* / Q000502:physiology; D001491:Basophils / Q000276:immunology*; D001773:Blood Cells; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D007073:Immunoglobulin E; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D053778:Thiazolidines / Q000494:pharmacology
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D053778:Thiazolidines; D015638:Cytochalasin D; D007073:Immunoglobulin E; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C037067:latrunculin A