Smooth muscle cells, dendritic cells and mast cells are sources of TNFalpha and nitric oxide in human carotid artery atherosclerosis.

Introduction: In atherogenesis, dendritic cells, beside presenting antigens, may be sources of tumour necrosis factor (TNF)alpha and nitric oxide (NO), together with mast cells and smooth muscle cells.

Material And Methods: We have looked at the expression of TNFalpha and inducible NO synthase (iNOs) by these cells by affinity cytochemistry in autoptical specimens from normal carotid arteries and not ruptured, hemorrhagic or calcified atheromata.

Results: Round to dendritic, major histocompatibility complex class II molecules (MHC-II+) cells and avidin-labeled mast cells were rare in normal arteries and significantly more numerous in atheromata. Many MHC-II+ cells expressed S-100 antigen; while a few were positive for phalloidin; appreciable fractions of these cells were immunoreactive for TNFalpha and iNOs, both in control specimens and atheromata. The fraction of mast cells labeled for iNOs was significantly lower in atheromata than in controls. Phalloidin positive cells were the most abundant cell type in the normal intima and atheromata; the fractions of these cells labeled for TNFalpha and iNOs were significantly higher in atheromata than in controls. Very few of these cells were also labeled for MHC-II. Computerized image analysis confirmed that the amounts of iNOs and TNFalpha were higher in atheromata than in controls. The increase in TNFalpha in atheromata was also confirmed by western blot.

Conclusions: Dendritic cells and mast cells can participate to the generation of TNFalpha and NO in the normal arterial wall and in atheromata, but myointimal cells are candidates as major sources of these molecules.