BIOPHYSICAL MECHANISMS IN LEUKOCYTES AND MELANOCYTES

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Studies are planned of phagocytic and non-phagocytic functions of leukocytes, that bear on aspects of the inflammatory response. The research plan is particularly aimed at the relationships among specific but overlapping areas of leukocyte activity: adherence, locomotion, target recognition, chemotaxis, penetration of endothelial monolayers, ingestion, the increased metabolic activity that ordinarily accompanies phagocytosis or other cell-triggering reactions, degranulation of lysosomal structures, 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 in a variety of ways to produce granule-poor anucleate fragments (cytoplasts) that retain motile and/or respiratory functions of the parent cell, 2) cytoplasts or leukocytes treated with agents that affect their killing capacity for microorganisms, 3) cytoplasts or leukocytes treated with molecules and particles that initiate calcium fluxes, activation of protein kinase C or of adenylate cyclase, protein phosphorylation, polymerization of microtubules and microfilaments, and rearrangements or altered expression of specific cell-surface receptors, 4) leukocytes treated with controlled brief heat to alter their respiratory burst oxidase activity, 5) leukocytes from patients with chronic granulomatous disease of childhood or other disorders of leukocyte structure and function, and 6) cytoplasts or leukocytes treated with substances that produce ultrastructural alterations in fibrillar elements, such as the metaphase-arresting agents, colchicine, vinblastine and griseofulvin (affecting microtubules), and cytochalasins (affecting microfilaments).