In vitro and ex vivo effect of RU41740 on human polymorphonuclear leukocyte function.
We investigated the effect of RU41740, a glycoprotein extracted from Klebsiella pneumoniae and possessing immunomodulating properties, on human neutrophil functions in vitro and ex vivo. Our in vitro results showed that RU41740 increased complement- and Fc receptor-dependent phagocytosis. Moreover, the drug enhanced the oxidative metabolism (assessed by chemiluminescence) both in resting and stimulated cells; in the latter case the RU41740-induced enhancement was observed when neutrophils were stimulated with opsonized particles of N-formyl-methionyl-leucyl-phenylalanine (FMLP) but not when phorbol myristate acetate was used. Using otherwise effective experimental conditions, RU41740 did not affect spontaneous or FMLP-induced neutrophil migration. For the ex vivo experience we tested neutrophils of ten elderly subjects with a previously demonstrated phagocytic defect. These subjects were treated orally with RU41740 at a daily dose of 2 mg for 1 week during the first month, and of 1 mg for 1 week in the second month. In this population, RU41740 was able to restore the impaired phagocytic activity and to induce a significant increase of spontaneous chemiluminescence (CL); stimulated CL was also positively influenced. These effects on neutrophils provide new explanatory bases for the immunostimulatory activity of RU41740.
Capsoni
F
F
Istituto di Medicina Interna, Malattie Infettive e Immunopatologia, University of Milan, Italy.
Minonzio
F
F
Venegoni
E
E
Ongari
A M
AM
Meroni
P L
PL
Guidi
G
G
Zanussi
C
C
D000276:Adjuvants, Immunologic / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D001426:Bacterial Proteins / Q000276:immunology / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; C037567:glycoprotein, Klebsiella pneumoniae