Dendritic cells, antibodies reactive with oxLDL, and inflammation.

Periodontitis appears to promote chronic inflammatory diseases, including atherosclerosis, but relevant mechanisms need clarification. Oral bacteria induce antibodies that bind not only bacteria, but also oxLDL. Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans induce remarkable IgG responses that are dominated by IgG2, and IgG2 is IFN-γ-dependent and is promoted by dendritic cells (DCs). LDL-reactive antibodies induced by P. gingivalis and A. actinomycetemcomitans include anti-phosphorylcholine (α-PC) and ß2-glycoprotein-1-dependent anticardiolipin (α-CL), and these antibodies may link chronic inflammatory diseases at a mechanistic level. Antibody-mediated uptake of oxLDL or bacteria dramatically enhances DC-IL-12, and DC-IL-12 induces NK-cell-IFN-γ responses that promote Th-1 responses and sustained inflammation. DCs may be derived from monocytes, and this is striking in cultures of aggressive periodontitis (AgP) monocytes, where DC numbers are about double control levels. Moreover, serum α-CL levels in individuals with AgP are frequently elevated, and these antibodies promote atherosclerosis in persons with antiphospholipid syndrome. Elevated serum levels of soluble-intercellular adhesion molecule, soluble-vascular cell adhesion molecule, and soluble-E-selectin are atherosclerosis-associated indicators of vascular inflammation, and these markers are elevated in the subset of AgP patients with high α-CL. We reason that periodontitis patients with elevated antibodies reactive with oxLDL could be a subgroup at high risk for cardiovascular sequelae.

Follicular dendritic cells stimulated by collagen type I develop dendrites and networks in vitro.

Follicular dendritic cells (FDCs) reside in germinal centers in which their dendrites interdigitate and form non-mobile networks. FDC purification requires the use of collagenase and selection columns and leaves FDCs without detectable dendrites when examined by light microscopy. We have reasoned that isolated FDCs might reattach to a collagen matrix, extend their processes, and form immobile networks in vitro. As a test for this, cells were plated on collagen type I, laminin, biglycan, and hyaluronan. After 12 h, 80%-90% of FDCs adhered to all tested matrices but not to plastic. Within 2 weeks, FDCs adhering to type I collagen had spread out and had begun to acquire processes with occasional interconnections. By day 30, most FDCs had fine processes that formed networks through interdigitation with neighboring cells. FDC identity was confirmed by FDC-M1 labeling, immune complex trapping, and retention by FDCs in the networks. Scanning electron microscopy confirmed that groups of FDCs were in networks composed of convolutions and branching dendrites emanating from FDC cell bodies. In vivo, collagen type I was co-localized with FDCs, 5 h after challenge of immune mice with antigen. However, 2 days later, the collagen type I fibers were largely found at the periphery of the active follicles. Flow cytometry established the expression of CD29 and CD44 on FDCs; this may have partly mediated FDC-collagen interactions. Thus, we report, for the first time, that FDCs attach to collagen type I in vitro and regenerate their processes and networks with features in common with networks present in vivo.