PMID- 3793326
OWN - NLM
STAT- MEDLINE
DCOM- 19870203
LR  - 20190908
IS  - 0192-0561 (Print)
IS  - 0192-0561 (Linking)
VI  - 8
IP  - 6
DP  - 1986
TI  - Clofazimine-mediated regulation of human polymorphonuclear leukocyte migration by 
      pro-oxidative inactivation of both leukoattractants and cellular migratory 
      responsiveness.
PG  - 605-20
AB  - The effects of clofazimine (0.15-20 micrograms/ml) on the spontaneous and 
      N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-stimulated migration, 
      membrane-associated oxidative metabolism, degranulation and production of 
      prostaglandin (PG) E2 by human polymorphonuclear in vitro have been investigated. 
      Clofazimine at concentrations of 0.3 microgram/ml and greater significantly 
      increased both the spontaneous and FMLP-stimulated chemiluminescence (CL), hexose 
      monophosphate shunt (HMS) activity, myeloperoxidase-mediated protein iodination, 
      auto-iodination, degranulation and PGE2 production by PMNL. At the same 
      concentrations clofazimine inhibited both random and leukoattractant-induced 
      migration of PMNL. Inhibition of PMNL migration by clofazimine was due to both a 
      cell-directed auto-oxidative mechanism and by functional inactivation of FMLP. 
      Clofazimine mediated inhibition of PMNL migration was prevented by the 
      anti-oxidants cysteine and dapsone but not by the potent inhibitors of PG 
      synthetase indomethacin and piroxicam. Anti-oxidants also protected FMLP from 
      functional inactivation by clofazimine-exposed PMNL. Clofazimine increased both 
      the spontaneous and FMLP-stimulated production of PGE2 by PMNL from four children 
      with chronic granulomatous disease (CGD). Clofazimine is not an oxidising agent 
      nor did it stimulate membrane-associated oxidative metabolism in CGD or 
      NaF-pulsed normal PMNL. These data show that clofazimine-mediated inhibition of 
      PMNL migration is dependent on intact cellular membrane-associated oxidative 
      metabolism. Clofazimine is therefore a pro-oxidative anti-inflammatory agent.
FAU - Anderson, R
AU  - Anderson R
FAU - Lukey, P
AU  - Lukey P
FAU - Van Rensburg, C
AU  - Van Rensburg C
FAU - Dippenaar, U
AU  - Dippenaar U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int J Immunopharmacol
JT  - International journal of immunopharmacology
JID - 7904799
RN  - 0 (Receptors, Formyl Peptide)
RN  - 0 (Receptors, Immunologic)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 8ZYQ1474W7 (Sodium Fluoride)
RN  - D959AE5USF (Clofazimine)
SB  - IM
MH  - Adult
MH  - Chemotaxis, Leukocyte/*drug effects
MH  - Clofazimine/*pharmacology
MH  - Humans
MH  - Kinetics
MH  - Luminescent Measurements
MH  - N-Formylmethionine Leucyl-Phenylalanine/metabolism/pharmacology
MH  - Neutrophils/drug effects/*physiology
MH  - Oxidation-Reduction
MH  - Pentose Phosphate Pathway/drug effects
MH  - Receptors, Formyl Peptide
MH  - Receptors, Immunologic/metabolism
MH  - Sodium Fluoride/pharmacology
EDAT- 1986/01/01 00:00
MHDA- 1986/01/01 00:01
CRDT- 1986/01/01 00:00
PHST- 1986/01/01 00:00 [pubmed]
PHST- 1986/01/01 00:01 [medline]
PHST- 1986/01/01 00:00 [entrez]
AID - 0192-0561(86)90033-0 [pii]
AID - 10.1016/0192-0561(86)90033-0 [doi]
PST - ppublish
SO  - Int J Immunopharmacol. 1986;8(6):605-20. doi: 10.1016/0192-0561(86)90033-0.