THE EFFECT OF INTERLEUKIN-8 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR ON THE RESPONSE OF NEUTROPHILS TO FORMYL-METHIONYL-LEUCYL-PHENYLALANINE
M. Mikami et al., THE EFFECT OF INTERLEUKIN-8 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR ON THE RESPONSE OF NEUTROPHILS TO FORMYL-METHIONYL-LEUCYL-PHENYLALANINE, Biochimica et biophysica acta. Molecular basis of disease, 1407(2), 1998, pp. 146-154
Neutrophils isolated from patients with chronic bronchitis and emphyse
ma have been shown to have enhanced responses to formyl peptides when
assessed in vitro compared to age, sex matched controls. It is current
ly unclear whether the observed differences are due to a 'priming' eff
ect by a second agent in vivo, or whether this is a primary difference
in the neutrophils, We have studied the effects of interleukin-8, whi
ch is thought to be one of the major pro-inflammatory cytokines in chr
onic lung disease and granulocyte macrophage colony stimulating factor
(GMCSF, in order to assess their effects on neutrophil chemotaxis and
connective tissue degradation. In addition, we have assessed the effe
ct of preincubation of these agents with neutrophils for 30 min follow
ed by stimulation with F-Met-Leu-Phe (FMLP) to investigate any possibl
e 'priming' effect that may he relevant to our clinical data. We repor
t suppression of neutrophil chemotaxis to FMLP following incubation of
the neutrophils with both IL-8 and GMCSF. However, we have observed a
n additive effect of IL-8 and FMLP for neutrophil degranulation leadin
g to fibronectin degradation. The results suggest that IL-8 does not '
prime' neutrophils for subsequent FMLP stimulation as observed in vivo
. Although the results for GMCSF were similar for the chemotactic resp
onse, the agent also had a synergistic effect on connective tissue deg
radation. However, it is concluded that neither agent could explain th
e enhanced neutrophil responses seen in our patients. (C) 1998 Elsevie
r Science B.V. All rights reserved.