MODULATION OF NEUTROPHIL MIGRATORY PATTERN AFTER IMMUNE COMPLEX STIMULATION.

CAROLINA GORLINO; FLORENCIA HARMAN; ROMINA RANOCCHIA; ALEJANDRA GARCÍA; GABRIEL MORÓN; BELKYS A. MALETTO; PETER HEERINGA; PISTORESI-PALENCIA, MARÍA CRISTINA

Mar del Plata

Congreso; LX Reunión de la Sociedad Argentina de Inmunología; 2012

Sociedad Argentina de Inmunología

Neutrophils recruited from the blood to inflammatory sites are key contributors to the nature of an immune response; however, their presence in chronic inflammatory sites, such as in immune complex (IC)-mediated autoimmune diseases, can be pathogenic. In this study we wanted to determine if IC-stimulation could modulate the expression of migratory molecules and receptors and, hence, drive neutrophil migration. We showed that after in vitro OVA/anti-OVA IC stimulation, murine neutrophils downregulated twofold the surface expression of CD62L (p˂0.05), whereas upregulated twofold their expression of LFA-1 (p˂0.05). Interestingly, IC also induced the expression of the chemokine receptor CXCR3 on neutrophils (p˂0.05). Additionally, we found that mRNA expression of sphingosine-1-phosphate (S1P) receptor S1PR4 was increased threefold in neutrophils stimulated with IC (p˂0.01). In parallel, we performed flow cytometric analysis in normal human blood samples to determine if IC could also regulate the expression of these migratory molecules on human neutrophils. We showed that a subset of CD16highCD62Llow neutrophils appeared after stimulation with heat aggregated IgG (HAGG). Moreover, this subpopulation showed to decrease threefold the expression of CXCR2, while upregulated two- and four-fold the expression of both CXCR3 and CD54, respectively, in comparison to the CD16highCD62Lhigh neutrophil subset (p˂0.01). When we investigated the signal pathways involved in the regulation of the surface expression of these molecules, we showed that the upregulation of CD54 on CD16highCD62Llow neutrophils was altered after rapamycin treatment (p˂0.05), showing that mTOR could be a signal pathway involved in the modulation of CD54 expression. Taken together, the results presented here demonstrated that the stimulation with IC modulate the expression of multiple intercellular adhesion molecules and receptors comprised in neutrophil trafficking.