Agonist-dependent failure of neutrophil function in diabetes correlates with extent of hyperglycemia

Linda M. McManus, Rebecca C. Bloodworth, Thomas J. Prihoda, Janet L. Blodgett, R. Neal Pinckard

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Inexplicable controversies with regard to possible functional defects of neutrophilic polymorphonuclear leukocytes (PMNs) in diabetes persist. The purpose of the present study was to elucidate the relative effectiveness of several PMN agonists in stimulating lysosomal-enzyme secretion and leukotriene (LT) B4 production by PMNs isolated from diabetic subjects. Formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) induced significantly less lysosomalenzyme secretion and LTB4 production in diabetic-subject PMNs than in normal-subject PMNs. It is surprising that PMNs from these same diabetic subjects responded normally after stimulation with A23187, serum-opsonized zymosan, or phorbol myristate acetate. The in vitro responsiveness of PMNs stimulated with fMLP or PAF was inversely correlated with indices of in vivo glycemic control (fasting plasma glucose and glycated-hemoglobin levels). In combination, these results indicate that hyperglycemia is associated with sustained decreases in PMN function but only in response to agonists that initiate stimulus-response coupling via G-protein-coupled receptors. This agonist-selective reduction in PMN responsiveness may contribute to the compromised host defense associated with sustained hyperglycemia in diabetes.

Original languageEnglish (US)
Pages (from-to)395-404
Number of pages10
JournalJournal of Leukocyte Biology
Volume70
Issue number3
StatePublished - 2001

Keywords

  • GPCR
  • Inflammation
  • LTB4
  • PAF
  • fMLP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Fingerprint Dive into the research topics of 'Agonist-dependent failure of neutrophil function in diabetes correlates with extent of hyperglycemia'. Together they form a unique fingerprint.

Cite this