Chemotactic migration triggers IL-8 generation in neutrophilic leukocytes

Rafat A. Siddiqui, Luke P. Akard, J. G.N. Garcia, Yi Cui, Denis English

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Neutrophils recovered from inflammatory exudates possess increased levels of IL-8, but exposure of neutrophils to chemoattractants results in only a modest stimulation of IL-8 generation. This study was undertaken to explore the hypothesis that IL-8 generation in these cells is dependent upon the process of migration. Neutrophils synthesized up to 30 times as much IL- 8 during migration in response to a gradient of diverse chemoattractants than they did when stimulated directly by the attractants in the absence of a gradient. This IL-8 response was dependent on migration since it was not observed in cells exposed to concentration gradients of chemoattractants under conditions that prevented cell movement. While actinomycin-D (1 μg/ml) had little influence on the generation of IL-8 during chemotaxis, the protein synthesis inhibitor cycloheximide (10 μg/ml) markedly blunted the accumulation of cell-associated IL-8, suggesting that new protein synthesis from preexisting mRNA was responsible for the effect. Consistent with this interpretation, migrating cells incorporated over 10 times as much [3H]leucine into IL-8 as did nonmotile neutrophils exposed to chemoattractants. A substantial portion of the IL-8 generated during chemotaxis was released upon subsequent metabolic stimulation. Thus, the IL- 8 synthesized during chemotaxis is uniquely positioned to exert a regulatory influence on inflammatory processes governed by neutrophilic leukocytes responding to inflammatory and infectious stimuli.

Original languageEnglish (US)
Pages (from-to)1077-1083
Number of pages7
JournalJournal of Immunology
Volume162
Issue number2
StatePublished - Jan 15 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Siddiqui, R. A., Akard, L. P., Garcia, J. G. N., Cui, Y., & English, D. (1999). Chemotactic migration triggers IL-8 generation in neutrophilic leukocytes. Journal of Immunology, 162(2), 1077-1083.