Neutrophil activation induced by ArtinM: release of inflammatory mediators and enhancement of effector functions.
The D-mannose binding lectin ArtinM from Artocarpus integrifolia, previously known as KM+ and artocarpin, is considered a stimulant of Th1-type immunity, which is able to confer resistance to some intracellular pathogens. In addition, ArtinM induces neutrophil migration by haptotaxis through simultaneous interactions of its carbohydrate recognition domains (CRDs) with glycans expressed on the extracellular matrix and the neutrophil surface. In the present study, we have expanded the characterization of ArtinM as a neutrophil activator. Exposure of neutrophils to ArtinM for 15 min resulted in tyrosine phosphorylation of intracellular proteins, a process that was selectively inhibited by d-mannose or mannotriose. Shortly after stimulation, neutrophils secreted high levels of LTB(4) and underwent shedding of L-selectin from their surface. Exposure to ArtinM enhanced neutrophil functions, such as respiratory burst and zymozan and Listeria monocytogenes phagocytosis. In addition, ArtinM-stimulated neutrophils displayed increased CXCL-8 secretion and TLR2 gene transcription. These results demonstrate that ArtinM is able to induce potent neutrophil activation, a feature that should be strongly considered in the assessment of the lectin capacity to confer resistance against infections.
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil.
Karina Alves
KA
Toledo
Carolina
C
Scwartz
Aline Ferreira
AF
Oliveira
Marina Cavalcanti Albuquerque Veiga
MC
Conrado
Emerson Soares
ES
Bernardes
Luiz Cláudio
LC
Fernandes
Maria Cristina
MC
Roque-Barreira
Gabriela
G
Pereira-da-Silva
Andréa Novais
AN
Moreno
D002465:Cell Movement; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D019041:L-Selectin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000276:immunology; D037241:Mannose-Binding Lectins / Q000494:pharmacology*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D037121:Plant Lectins / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D016209:Interleukin-8; D037241:Mannose-Binding Lectins; D037121:Plant Lectins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C090683:artocarpin lectin; D019041:L-Selectin; D007975:Leukotriene B4