Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by monocytes and large granular lymphocytes stimulated with Mycobacterium avium-M. intracellulare: activation of bactericidal activity by GM-CSF

Abstract

Treatment of monocytes with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to enhance their antimycobacterial activity in an in vitro assay. Furthermore, Mycobacterium avium-M. intracellulare was found to induce the production of this hemopoietic growth factor. Human peripheral blood mononuclear cells were fractionated by plastic adherence and Percoll density centrifugation, and each population of cells was stimulated with mycobacteria. GM-CSF was produced by both monocytes and large granular lymphocytes (LGL) but not T lymphocytes. The phenotype of the GM-CSF-producing LGL was found to be CD2+, CD16+, and HLA-DR+ but negative for T-cell and monocyte markers. Kinetic studies demonstrated that GM-CSF appeared in the supernatant fluids within 2 days of culture of either monocytes or LGL and continued to be produced up to 7 days of incubation. Northern (RNA) blot analysis of RNA from both cell types demonstrated the expression of GM-CSF message within 24 h of stimulation. From these studies, LGL and monocytes are capable of responding to M. avium-M. intracellulare by producing factors that augment normal immune functions, including the antibacterial capability of monocytes.

Suppression of granulocyte/macrophage colony‐stimulating factor release from human monocytes by cyclic AMP‐elevating drugs: role of interleukin‐10

“…In the present study we have confirmed previous investigations that human peripheral blood monocytes release the haematopoietic pro‐inflammatory cytokine, GM‐CSF in response to bacterial LPS (Blanchard et al ., 1991; de Waal Malefyt et al ., 1991; Meja et al ., 2000). In addition, we have extended this finding by providing evidence that cyclic AMP‐elevating drugs act at both the transcriptional and post‐transcriptional level to suppress GM‐CSF output by a mechanism that is not mediated by IL‐10.…”

“…Granulocyte/macrophage colony‐stimulating factor (GM‐CSF) is a 14 – 35 kDa acidic glycoprotein that is secreted by many cells including those of the human monocyte/macrophage lineage (Blanchard et al ., 1991; Meja et al ., 2000; Sallerfors & Olofsson, 1992). Many studies, in vitro and in vivo , have shown that GM‐CSF primes and activates a wide variety of inflammatory and immune cells and is implicated in the pathogenesis of a number of respiratory diseases including chronic obstructive pulmonary disease (COPD) and asthma.…”

Processing of mycobacterial lipids and effects on host responsiveness

“…Although a comprehensive understanding of M. avium 's pathogenesis has not yet evolved, it can be concluded that the initial interaction of the immune system with M. avium is multifactorial (1,76,77). Cytokine responses that have been evaluated include IL-1 alpha, IL-1 beta, IL-6, IL-10, TNF-alpha, and TGF-beta (57,78,79,80,81,82,83). Other studies report an immunosuppressive capacity of M. avium associated with prostaglandin E 2 (PGE 2 ) (84,85,86,87,88).…”

p38 MAP kinase and MKK‐1 co‐operate in the generation of GM‐CSF from LPS‐stimulated human monocytes by an NF‐κB‐independent mechanism

“…Granulocyte/macrophage colony‐stimulating factor (GM‐CSF) is a variably glycosylated cytokine produced by many cells including those of the human monocyte/macrophage lineage ( Blanchard et al ., 1991 ; Sallerfors & Olofsson, 1992 ). GM‐CSF is implicated in a number of respiratory diseases including asthma ( Broide et al ., 1991 ; 1992a , 1992b ; Brown et al ., 1991 ; Davies et al ., 1995 ; Hallsworth et al ., 1994 ; Lai et al ., 1996 ; Lei et al ., 1998 ; Nakamura et al ., 1993 ; Sousa et al ., 1993 ; Till et al ., 1995 ; Woolley et al ., 1995 ; Xing et al ., 1996 ) where it is a potent pro‐inflammatory stimulus.…”