Human basophilic leukocytes and mast cells are markedly pro-inflammatory cells that release a number of chemical mediators, including histamine and SRS-A, after immunologic stimulation involving cross-linking of cell surface-bound IgE molecules. Although numerous studies have been performed using human lung parenchymal fragments containing a mixture of cell types, and rodent cells, detailed biochemical and immunologic studies have not been performed using purified human mast cells. Recently, we have developed a technique for the purification of human lung mast cells to purities of greater than 95% by enzymatic dispersion, centrifugation by countercurrent elutriation, and immunoaffinity chromatography. Using purified preparations of these cells, we plan to quantitate mediators of inflammation produced by these cells including SRS-A, prostaglandins, and lysosomal hydrolases; quantitate the lipoxygenase products of arachidonic acid produced by these cells and determine the role of these products in histamine release; explore biochemical mechanisms involved in mediator release from these cells; and explore methods for the pharmacologic control of these pro-inflammatory cells. Such studies promise not only to provide important information concerning the cell biology and biochemistry of human lung mast cells, but also information about pulmonary disease states such as bronchial asthma and chronic inflammatory disorders that are likely due, at least in part, to the inflammatory process and inflammatory mediators.

K08HL001974

1986-07-01

1987-06-30