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Expression of adhesion molecules and functional stimulation in human neutrophils: modulation by GM‐CSF and role of the Bcr gene
Author(s) -
Novella Annunziata,
Bergamaschi Gaetano,
Canale Claudia,
Fossati Gianluca,
Gritti Donatella,
Lucotti Claudia,
Mazzone Antonino,
To Laura,
Cazzola Mario
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.2503067.x
Subject(s) - respiratory burst , cd18 , chemotaxis , integrin alpha m , superoxide , biology , cell adhesion molecule , microbiology and biotechnology , gene expression , phagocytosis , integrin , stimulation , receptor , n formylmethionine leucyl phenylalanine , chemistry , immunology , gene , biochemistry , flow cytometry , endocrinology , enzyme
Although devoid of proliferative capacity, polymorphonuclear neutrophils (PMN) express receptors for haemopoietic growth factors and need growth factors for survival and functional stimulation. This study showed that in vitro treatment of human PMN with GM‐CSF for up to 48 h increases cell surface expression of the β2‐integrin molecules CD11b/CD18 and CD11c/CD18 and of the receptor for the chemotactic peptide fMLP. Such modifications are usually expression of PMN activation. PMN treated with GM‐CSF also displayed increased phagocytosis of latex particles and enhanced oxidative burst and superoxide anion release. Since integrins mediate PMN adhesion to endothelium, homotypic adhesion, chemotaxis/phagocytosis and the triggering of respiratory burst, our results suggested that functional stimulation of PMN persisted following prolonged exposure of PMN to growth factors and that it was not a temporary phenomenon which lasted only for the first 12–24 h of treatment. We also used oligonucleotides antisense to the Bcr gene mRNA to inhibit expression of the gene and evaluate its function in PMN, following the recent observation that PMN from Bcr‐null mutant mice produced increased amounts of reactive oxygen metabolites upon activation. The antisense oligonucleotides had no effect on the parameters investigated. This may indicate that increased production of O − 2 by neutrophils in which the Bcr gene is not expressed requires either that gene expression is absent in the earlier stages of myeloid differentiation/maturation, so that when inhibition occurs in the terminally differentiated neutrophils their functional status is no longer influenced, or that the residual low‐level expression of the gene which may be present in the antisense‐treated cells is sufficient to provide a normal response to stimulation.