Path Mechanisms I 4: Macrophages, Destruction of Collagen and PDL, Periostat Flashcards
If macrophages provide the cytokines that eventually cascade into bone resorption; then what calls in the macrophages?
LPS reacts directly with Toll Like Receptors on macrophages (Innate Immunity)
Where is the source of cytokines in the adaptive immune response?
Activated T-Cells produce INF-gamma, which activates macrophages
But still, if LPS interacts with TLRs, how do the Macrophages get to the Periodontium in order to bind with the LPS?
The presence of Gram (-) bacteria also activates complement which allows for macrophage chemotaxis
What does Aa stand for in terms of inflammatory response?
Arachidonic acid metabolites (prostaglandins)
Where is the evidence for this Macrophage Pathogensis theory?
Macrophages from patients with chronic PD secrete higher levels of TNF-alpha with stimulated with LPS in vitro. Some studies show the same with IL-1B
Where else in the periodontium can the levels of IL-1 and TNF-alpha be elevated?
Crevicular fluid
Peripheral blood
What about evidence that AA metabolites play a role in tissue destruction?
NSAIDs can slow the rate of alveolar bone resorption (They indirectly inhibit PGE2)
Macrophages from patients with Severe PD secrete higher levels of PGE2 when stimulated with LPS in vitro
How is collagen/pdl destroyed?
Macrophages also secrete MMP-1 which has collagenase activity
What is periostat?
Low dose doxycycline
What does periostat accomplish?
Too low of a dose to kill bacteria but in inhibits MMP-1 activity to protect/slow collagen degredation.
What other cells can secrete MMPs?
Fibroblasts
PMNs
What does OPG bind to?
It also binds to RANK-L
What does OPG do?
It stops the bone resorption path and pushes the equilibrium towards bone formation
What is the enzyme that changes As metabolites into Prostaglandins?
Cyclooxygenase
What OTC drug inhibits Cyclooxygenase?
NSAIDs (Advil)
