The effects of a single intraperitoneal injection of polyamino acids (lysine, glutamic, aspartic) on mast cells of the rat are described. In vitro interaction of mast-cell components with these polyamino acids is also explored. Poly-DL-lysine (but not the acidic amino acids) has both immediate (minutes-hours) and long-term (days-weeks) effects on mast cells. At the dosage selected, some cells evidence rapid fusion of granules and degranulation, but without concomitant swelling; most display intracellular changes only. Neither degranulation nor granule fusion appears to be lethal. Rather, these spur the cell to greater synthetic activity which involves first the Golgi apparatus and subsequently also the endoplasmic reticulum. Early involvement of macrophages and eosinophils is described. Sequential studies after polylysine injection support the following concepts: (a) mast-cell granules exist as "physiological sets," several being confined to a common membranous "sac;" (b) each set can respond independently to applied stimuli; (c) each set can connect directly to the extracellular milieu; (d) poly-DL-lysine binds directly to the granules and stabilizes them; it is not readily digested; (e) mast-cell granules are produced directly; they do not arise by intake of exogenous polysaccharides. It is hypothesized that mast-cell granules are topologically outside the cell while held intimately within extensive cytoplasmic folds and recesses. Mast cells may function by causing intercellular connective tissue fluids to percolate over their granules which may process this fluid in some as yet undefined way(s).

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