Leukocyte chemotaxis in vivo. II. Analysis of the selective inhibition of neutrophil or mononuclear cell accumulation

R. J. Perper, M. Sanda, G. Chinea, A. L. Oronsky

Research output: Contribution to journalArticlepeer-review

Abstract

A new model for quantitating chemotaxis in vivo was used to analyze the effect of various agents on the chemotactic response of the neutrophil as well as the nonlymphocytic mononuclear cell. The technique used involves adoptively transferring 51Cr isologous rat leukocytes and measuring their accumulation in a carrageenin-induced inflammatory reaction. The accumulation of labeled neutrophils and mononuclear cells was measured 5 hours and 18 hours, respectively, after the injection of labeled cells. Drugs were given either parenterally to the recipients or incubated with the cells in vitro prior to adoptive transfer. Using both methods, methylprednisolone inhibited the chemotaxis of both mononuclear cells and neutrophils. It also inhibited neutrophil chemotaxis when measurement of chemotaxis was made in vitro. Colchicine and vinblastine inhibited neutrophil but not mononuclear cell chemotaxis, whereas parenteral administration of dibutyryl cAMP enhanced only neutrophil chemotaxis. Drugs which are reported to alter the integrity of cell membranes (phenylbutazone, indomethacin, flufenamic acid, and chlorpromazine) all inhibited mononuclear cell but not neutrophil chemotaxis. At the concentrations and doses used the drugs did not alter the circulation of the adoptively transferred cells. Neither chloroquine, cyclophosphamide, nor clonidine (a hypotensive agent) affected chemotaxis. The results confirmed the specificity of the methods used for quantitating chemotaxis in vivo for two cell types by showing selective inhibition at the level of the cell itself and possibly at the level of the chemotactic stimuli, since depletion of total hemolytic complement with cobra venom factor inhibited neutrophil chemotaxis. The data derived from experiments using pharmacologic agents suggest that the chemotaxis of adoptively transferred neutrophils is dependent upon intact microtubular function, whereas mononuclear cell chemotaxis may be sensitive to alteration of the cell surface.

Original languageEnglish (US)
Pages (from-to)394-406
Number of pages13
JournalThe Journal of laboratory and clinical medicine
Volume84
Issue number3
StatePublished - Sep 1974

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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