Is. Yuen et al., TIME-COURSE OF CHEMOTACTIC FACTOR GENERATION AND NEUTROPHIL RECRUITMENT IN THE LUNGS OF DUST-EXPOSED RATS, American journal of respiratory cell and molecular biology, 15(2), 1996, pp. 268-274
The time course of neutrophil recruitment into the lung, neutrophilic
chemotactic activity, and the gene expression of neutrophilic chemokin
es by lavaged cells was determined after intratracheal instillation of
various particles. Low-toxicity, low-solubility dusts such as titaniu
m dioxide (TiO2) particles, as well as fibrogenic crystalline silica a
nd nonfibrogenic amorphous silica particles were instilled into the lu
ngs of rats. Results showed that all three dusts induced neutrophilic
inflammation as early as 5 h after exposure. Both crystalline and amor
phous silica elicited higher degrees of pulmonary inflammation when co
mpared with TiO2 particles. Maximal infiltration of neutrophils into t
he lungs occurred 5 to 6 h after intratracheal instillation of the dus
ts. The inflammatory response was transient for TiO2 and amorphous sil
ica, i.e., evident at 2 days after exposure but not different from con
trols at 10 days after exposure. In contrast, inflammatory effects wer
e sustained through a 10-day period following exposures to crystalline
silica. Chemotactic activity for neutrophils was detected directly in
bronchoalveolar lavage (BAL) fluids of dust-exposed rats within 2 h a
fter exposure, but not in the BAL fluids of saline- or unexposed rats.
The chemotactic activity was correlated with the influx and disappear
ance of neutrophils into alveolar regions of the lung in TiO2- and amo
rphous silica-exposed rats. The mRNA expression of two known neutrophi
l chemotactic cytokines in BAL cells, macrophage inflammatory protein-
2 (MIP-2) and KC, also correlated with chemotactic activity and acute
pulmonary inflammatory responses. MIP-2 mRNA was expressed prior to th
e detection of chemotactic activity in BAL fluids. However, the mRNA e
xpressions of MIP-2 and KC were transient for rats that were exposed t
o these dusts as KC and MIP-2 message were no longer detectable in BAL
cells after 2 days of recovery. Although both neutrophilic chemotacti
c activity and inflammation remained prominent 10 days after exposure
to crystalline silica, MIP-2 expression could not be detected in BAL c
ells. Thus, we conclude that MIP-2 is likely to be only one of several
cytokines involved in mediating neutrophilic inflammation following a
single instillation of crystalline silica.