Immunization with the adjuvant MF59 induces macrophage trafficking and apoptosis.

The mechanisms associated with the immunostimulatory activity of vaccine adjuvants are still poorly understood. We have undertaken a study to determine whether antigen-presenting cell trafficking is modified by administration of the submicron emulsion adjuvant MF59. We investigated the fate of inflammatory macrophages after intramuscular injection of the antigen herpes simplex virus gD2 with fluorescence-labeled MF59. A homogeneous population of macrophages infiltrated the muscle, internalized adjuvant and expressed markers characteristic of mature macrophages over a 48-h period. Macrophage influx to the injection site was reduced by 70% in mice deficient for the chemokine receptor 2 (CCR2). Two distinct cell populations were shown to contain fluorescence-labeled MF59 in the draining lymph node at 48 h post injection. The first population had a round morphology, exhibited bright fluorescence, was located in the subcapsular sinus, and was apoptotic. The second population had a dendritic morphology, was weakly fluorescent, and was located in the T cell area where adjuvant-containing apoptotic bodies identified by TUNEL labeling were present. We propose that lymph node-resident dendritic cells can acquire antigen and MF59 after intramuscular immunization by uptake of the apoptotic macrophages.

Microvascular remodelling in chronic airway inflammation in mice.

1. Chronic inflammation is associated with blood vessel remodelling, including vessel proliferation and enlargement, and changes in vessel phenotype. We sought to characterize these changes in chronic airway inflammation and to determine whether corticosteroids that inhibit inflammation, such as dexamethasone, can also reduce microvascular remodelling. 2. Chronic airway inflammation was induced in C3H mice by infection with Mycoplasmapulmonis and the tracheal vessels treatment also decreased the immunoreactivity for P-selectin and the number of adherent leucocytes (595 +/- 203 vs 2,024 +/- 393 cells/ mm2 in treated and non-treated infected mice, respectively). 6. We conclude that microvascular enlargement and changes in vessel phenotype are features of some types of chronic inflammation and, furthermore, that dexamethasone reverses the microvascular enlargement, changes in vessel phenotype and leucocyte influx associated with chronic inflammatory airway disease.