Studies on leucocyte-drug interaction with benoxaprofen.

Studies of the preferential action of benoxaprofen on the movement of mononuclear leucocytes have been extended to include human cells, and the positive correlation between human and animal findings is discussed. Benoxaprofen also affected the increased response of the hexose monophosphate (HMP) shunt of rat mononuclear cells stimulated by addition of latex particles but did not inhibit the same metabolic pathway in polymorphonuclear cells. The small effects on phagocytosis by unelicited mononuclear cells did not correlate with the partial inhibition of their HMP shunt by benoxaprofen. Attempts to explain these findings in terms of drug binding were undertaken. High affinity and low affinity binding of benoxaprofen to mononuclear and polymorphonuclear cells were found to occur. Overall, the amount of benoxaprofen bound to mononuclear cells was greater than that bound to polymorphonuclear cells.

Replenishment of alveolar macrophages in silicosis: implication of recruitment by lipid feed-back.

The deposition of quartz in the pulmonary alveoli creates a major demand for macrophages to replace those destroyed, but local proliferation of monocytes appeared to be minimal and the role of systemic recruitment was therefore explored. Injected silica and lipids stimulated the phagocytic function of the mononuclear phagocytic system (MPS), whilst inhaled silica provoked lipid accumulation in the lung, thus suggesting that lipid might also induce a proliferative response in the marrow. Using marrow cultures, cells of the rat MPS were identified by size and phagocytic capacity for latex microspheres, and then subjected to kinetic analysis in litter-mate pairs by single and double labelling autoradiography, under normal conditions and after administration of lipid extracted from rat lungs consolidated by silica-induced alveolar lipo-proteinosis. Treatment of the results by a new device facilitated distinction of promonocytes from monocytes and thus afforded a more precise means of assessing MPS kinetics. The duration of DNA synthesis and the cell-cycle time of promonocytes were reduced and the rate of entry into DNA synthesis increased as a result of i.v. injection of lung lipid. These findings support the involvement of systemic recruitment of monocytes from the marrow by a positive feed-back mechanism when a powerful irritant persists in the lungs and the results are discussed in the overall context of silicotic fibrogenesis.