RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs)

Kate S. Collison, Ranjit S. Parhar, Soad S. Saleh, Brian F. Meyer, Aaron A. Kwaasi, Muhammad M. Hammami, Ann Marie Schmidt, David Stern, Futwan A. Al-Mohanna

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The accumulation of advanced glycation end products (AGEs) in the tissue and serum of subjects with diabetes has been linked to the pathogenesis of vascular complications. Because diabetes may be also complicated by increased susceptibility to recurrent infection, we investigated the effects of AGEs on human neutrophils, because their burst of activity immediately upon engagement of pathogens or other inflammatory triggers is critical to host response. We demonstrate the presence of receptor for advanced glycation end products (RAGE) at the message and protein levels. We also demonstrate that AGE albumin (but not control albumin) binds with high affinity to human neutrophils (Kd of 3.7±0.4 nM). The binding was blocked almost completely by excess soluble RAGE, anti-RAGE antibodies, or antibodies to CML-modified albumin. AGE albumin induced a dose-dependent increase in intracellular-free calcium as well as actin polymerization. Further, AGE albumin inhibited transendothelial migration and Staphylococcus aureus-induced but not fMLP-induced production of reactive oxygen metabolite. Moreover, although AGE albumin enhanced neutrophil phagocytosis of S. aureus, it inhibited bacterial killing. We conclude that functional RAGE is present on the plasma membrane of human neutrophils and is linked to Ca2+ and actin polymerization, and engagement of RAGE impairs neutrophil functions.

Original languageEnglish (US)
Pages (from-to)433-444
Number of pages12
JournalJournal of Leukocyte Biology
Volume71
Issue number3
StatePublished - Mar 1 2002
Externally publishedYes

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Advanced Glycosylation End Products
Albumins
Neutrophils
Polymerization
Staphylococcus aureus
Actins
Transendothelial and Transepithelial Migration
Antibodies
Phagocytosis
Blood Vessels
Advanced Glycosylation End Product-Specific Receptor
Cell Membrane
Oxygen
Calcium
Infection
Serum
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cell Biology

Cite this

Collison, K. S., Parhar, R. S., Saleh, S. S., Meyer, B. F., Kwaasi, A. A., Hammami, M. M., ... Al-Mohanna, F. A. (2002). RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs). Journal of Leukocyte Biology, 71(3), 433-444.

RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs). / Collison, Kate S.; Parhar, Ranjit S.; Saleh, Soad S.; Meyer, Brian F.; Kwaasi, Aaron A.; Hammami, Muhammad M.; Schmidt, Ann Marie; Stern, David; Al-Mohanna, Futwan A.

In: Journal of Leukocyte Biology, Vol. 71, No. 3, 01.03.2002, p. 433-444.

Research output: Contribution to journalArticle

Collison, KS, Parhar, RS, Saleh, SS, Meyer, BF, Kwaasi, AA, Hammami, MM, Schmidt, AM, Stern, D & Al-Mohanna, FA 2002, 'RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs)', Journal of Leukocyte Biology, vol. 71, no. 3, pp. 433-444.
Collison KS, Parhar RS, Saleh SS, Meyer BF, Kwaasi AA, Hammami MM et al. RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs). Journal of Leukocyte Biology. 2002 Mar 1;71(3):433-444.
Collison, Kate S. ; Parhar, Ranjit S. ; Saleh, Soad S. ; Meyer, Brian F. ; Kwaasi, Aaron A. ; Hammami, Muhammad M. ; Schmidt, Ann Marie ; Stern, David ; Al-Mohanna, Futwan A. / RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs). In: Journal of Leukocyte Biology. 2002 ; Vol. 71, No. 3. pp. 433-444.
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