PMID- 24667630
OWN - NLM
STAT- MEDLINE
DCOM- 20150209
LR  - 20211021
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Print)
IS  - 1073-2322 (Linking)
VI  - 42
IP  - 1
DP  - 2014 Jul
TI  - Itraconazole, a commonly used antifungal, inhibits Fcgamma receptor-mediated 
      phagocytosis: alteration of Fcgamma receptor glycosylation and gene expression.
PG  - 52-9
LID - 10.1097/SHK.0000000000000169 [doi]
AB  - Itraconazole (ICZ) is commonly used for the treatment of fungal infections, 
      particularly in immunocompromised patients. In addition, ICZ has been recently 
      found to have antiangiogenic effects and is currently being tested as a new 
      chemotherapeutic agent in several cancer clinical trials. We have previously 
      shown that ICZ impaired complex N-linked glycosylation processing, leading to the 
      accumulation of high-mannose glycoproteins on the surface of macrophages (Mos). 
      This investigation was directed at determining the effects of ICZ on phagocytosis 
      as a major function of Mos. We found a significant decrease in the phagocytosis 
      of opsonized bacterial particles in ICZ-treated murine Mos in comparison with 
      nontreated Mos. Furthermore, the impairment of phagocytosis was associated with a 
      decrease in cell surface expression of Fcgamma receptors (FcgammaRs) as well as 
      alteration of their glycosylation pattern. Concomitantly, a reduction in all 
      three isoforms of the FcgammaR family (i.e., Fcgr1, Fcgr2, and Fcgr3) mRNA levels was 
      observed after incubation with ICZ. The effect of ICZ on phagocytosis and FcgammaR 
      expression was reversed by addition of low-density lipoprotein. These studies 
      indicate that ICZ treatment certainly has a dramatic effect on macrophage 
      function, which could result in a potential impairment of the immune system';s 
      ability to respond to pathogens and may lead to an elevated incidence of 
      infections.
FAU - Nino, Diego F
AU  - Nino DF
AD  - *Biomedical Sciences Graduate Program,Departments of daggerSurgery and double daggerNeurosciences 
      and  section signThe Center for Investigations of Health and Education Disparities, 
      University of California, San Diego, La Jolla, California.
FAU - Cauvi, David M
AU  - Cauvi DM
FAU - De Maio, Antonio
AU  - De Maio A
LA  - eng
GR  - F31 GM090681/GM/NIGMS NIH HHS/United States
GR  - R25 GM083275/GM/NIGMS NIH HHS/United States
GR  - R01 GM083275/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Antifungal Agents)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Receptors, IgG)
RN  - 304NUG5GF4 (Itraconazole)
SB  - IM
MH  - Animals
MH  - Antifungal Agents/administration & dosage/*pharmacology
MH  - Cell Membrane/metabolism
MH  - Cells, Cultured
MH  - Cholesterol, LDL/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Escherichia coli/immunology
MH  - Gene Expression Regulation/drug effects/immunology
MH  - Glycosylation/drug effects
MH  - Itraconazole/administration & dosage/antagonists & inhibitors/*pharmacology
MH  - Macrophages/drug effects/immunology
MH  - Male
MH  - Mice, Inbred Strains
MH  - Phagocytosis/*drug effects
MH  - Receptors, IgG/*antagonists & inhibitors/genetics/metabolism
PMC - PMC4071940
MID - NIHMS573772
EDAT- 2014/03/29 06:00
MHDA- 2015/02/11 06:00
PMCR- 2015/07/01
CRDT- 2014/03/27 06:00
PHST- 2014/03/27 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2015/02/11 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - 10.1097/SHK.0000000000000169 [doi]
PST - ppublish
SO  - Shock. 2014 Jul;42(1):52-9. doi: 10.1097/SHK.0000000000000169.