Studies are planned of phagocytic and non-phagocytic functions of (especially polymorphonuclear) leukocytes, that bear on aspects of the acute inflammatory response. The research plan is particularly aimed at the relationships among specific but overlapping areas of leukocyte activity: locomotion, orientation, target recognition, ingestion, the increased metabolic activity that ordinarily accompanies phagocytosis or other cell-triggering reactions, degranulation of lysosomal structures in leukocytes, and intracellular killing. The ways in which these activities can be separated from one another may distinguish obligate interactions from mere concomitance, and may reveal the specific pathways by which cell function is altered. The experimental approach is through various agents and situations in which one or more of these activities appear to be altered, including 1) leukocytes treated to produce anucleate, motile, cytoplasmic fragments, 2) leukocytes treated with molecules and particles that bind to Fc receptors; with hormones and other agents designed to alter intracellular levels of cyclic nucleotides; and with membranolytic crystals such as silica or urate, 3) leukocytes from patients with chronic granulomatour disease of childhood, and 4) leukocytes treated with substances that produce ultrastructural alterations in fibrillar elements, such as the metaphase-arresting agents, colchicine and vinblastine (affecting microtubules), and cytochalsin B (affecting microfilaments). From the viewpoint of comparative cell function, certain of the last group of substances are also considered as they affect such functions in other cells as the movement of melanin granules in melanocytes, and the organization of the mitotic spindle in dividing cells.
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