Neutrophil activation induced by the lectin KM+ involves binding to CXCR2.
The lectin KM+ from Artocarpus integrifolia, also known as artocarpin, induces neutrophil migration by haptotaxis. The interactions of KM+ with both neutrophils and the extracellular matrix depend on the lectin's ability to recognize mannose-containing glycans. In the present study, we characterized the binding of KM+ to human neutrophils and the responses stimulated by this binding. Exposure to KM+ results in cell polarization, formation of a lamellipodium, and induction of deep ruffles on the cell surface. By fluorescence microscopy, we observed that KM+ is distributed homogeneously over the cell surface. KM+/ligand complexes are rapidly internalized, reaching maximum intracellular concentrations at 120 min, and decreasing thereafter. Furthermore, KM+ binding to the surface of human neutrophils is inhibited by the specific sugars, d-mannose or mannotriose. KM+-induced neutrophil migration is inhibited by pertussis toxin as well as by inhibition of CXCR2 activity. These results suggest that the KM+ ligand on the neutrophil surface is a G protein-coupled receptor (GPCR). The results also suggest that neutrophil migration induced by KM+ involves binding to CXCR2.
Pereira-da-Silva
Gabriela
G
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.
Moreno
Andréa N
AN
Marques
Fabiana
F
Oliver
Constance
C
Jamur
Maria Célia
MC
Panunto-Castelo
Ademilson
A
Roque-Barreira
Maria Cristina
MC
D002462:Cell Membrane; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity; D006801:Humans; D008024:Ligands; D037241:Mannose-Binding Lectins / Q000378:metabolism / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D037121:Plant Lectins / Q000378:metabolism / Q000494:pharmacology*; D011554:Pseudopodia; D043562:Receptors, G-Protein-Coupled; D023063:Receptors, Interleukin-8B / Q000378:metabolism*
D008024:Ligands; D037241:Mannose-Binding Lectins; D037121:Plant Lectins; D043562:Receptors, G-Protein-Coupled; D023063:Receptors, Interleukin-8B; C090683:artocarpin lectin