DISCUSSION part 2

To our knowledge, the only previously detailed report on the density of HLA-D region antigens on alveolar macrophages is that of Campbell et al who studied HLA-DR. Our study confirms that levels of HLA-DR on alveolar macrophages in sarcoidosis are slightly increased compared with normal; and it also shows that levels are within the normal range in patients with nongranulomatous fibrosing lung dis­eases where lavage lymphocyte increases are much less common. However, we observed even more significant increases in levels of HLA-DQ and DP on alveolar macrophages in sarcoidosis. HLA-DQ and DP were also strikingly increased on alveolar macrophages in EAA, which is another granulomatous lung disease associated with strikingly increased numbers of T lymphocytes in lavage samples. Thus, we suggest that enhanced expression of HLA-D region antigens on alveolar macrophages, in particular HLA-DQ and DP, may be involved in the mechanisms leading to enhanced antigen-presenting function and T-cell pro­liferation within the lungs not only in sarcoidosis but also in EAA.

Our observation of a significant inverse correlation between HLA-DQ levels on alveolar macrophages and lung function in sarcoidosis suggests that monitoring these levels may provide a marker of disease activity. Indeed, there has been a report that the percentages of alveolar macrophages expressing HLA-DQ mole­cules are higher in “active” compared with “inactive” sarcoidosis or normal control subjects. suhagra 100

Possible reasons for the enhanced levels of HLA-D region antigens in patients with sarcoidosis include evidence that T lymphocytes from the lungs of these patients spontaneously secrete interferon gamma.This mediator is known to be capable of enhancing la expression on various cell types, including alveolar macrophages. Furthermore, it has been reported that the capacity of alveolar macrophages in sarcoidosis to release the prostaglandin PGE2 is reduced com­pared with normal alveolar macrophages. This may also favor the expression of high levels of HLA-D region products on alveolar macrophages since PGE2 can suppress la expression and suppress lympho­proliferative responses. PGE2 is also capable of inhibiting granuloma formation in animal models of granulomatous lung disease. However, in considering the possible role of PGE2 it needs to be explained why normal alveolar macrophages produce less PGE2 than normal blood monocytes, yet they have compara­tively poor antigen-presenting capacity. Information on interferon gamma and PGE2 production by cells in lavage samples from patients with EAA is not yet available.

There is much less known about the regulation and function of HLA-DQ and DP on immunocompetent cells than HLA-DR. However, it has been reported that interferon gamma is capable of enhancing HLA- DQ as well as DR expression. It has also been reported that the small number of strongly HLA-DQ or DP positive mononuclear cells in human blood may be especially efficient in antigen-presenting function.Whether the increased numbers of monocytes re­cruited to the lungs of patients with sarcoidosis might be selectively HLA-DQ or DP positive cells is not known. Studies are now needed to explore these suggestions and to determine the functional capacity of alveolar macrophages in sarcoidosis and EAA to present antigens in relation to the levels of HLA-DQ and DP they express. The potential implications for immunotherapy can then be considered. In contrast with the granulomatous lung diseases, we have found no evidence of increased levels of HLA-D region antigens on alveolar macrophages obtained by lavage from the lungs of patients with С FA or FA associated with scleroderma. Increases in granulocytes are more common than lymphocytes in the lavage samples of these patients. This suggests that the increased numbers of lymphocytes that are detectable within the alveolar walls and septa in lung biopsy specimens of such patients may be stimulated by accessory cells that are located in the interstitium and not accessible by lavage. cialis soft tabs online

In conclusion, our findings suggest that elevated levels of HLA-DQ and DP on alveolar macrophages in sarcoidosis and EAA may be more relevant than HLA-DR in the mechanisms leading to immune hyperreactivity in these granulomatous lung diseases. In support of this hypothesis, levels of HLA-DQ and DP correlated more closely than HLA-DR with the counts of lymphocytes in lavage in sarcoidosis, and HLA-DQ levels correlated with proportions of lym­phocytes in proliferation. Levels of HLA-DQ also correlated significantly with the extent of lung func­tional impairment.