TY - JOUR
T1 - Eosinophils and monocytes produce pulmonary and activation-regulated chemokine, which activates cultured monocytes/macrophages
AU - Schraufstatter, Ingrid
AU - Takamori, Hiroshi
AU - Sikora, Lyudmila
AU - Sriramarao, P.
AU - DiScipio, Richard G.
PY - 2004/3
Y1 - 2004/3
N2 - Pulmonary and activation-regulated chemokine (PARC/CCL18) belongs to the family of CC chemokines and shares 61% sequence identity with monocyte inflammatory protein (MIP)-1α. Produced by dendritic cells and macrophages primarily in the lung, PARC is known to be chemotactic for T cells. Because PARC's biological function is largely unknown, we screened various leukocyte populations for PARC expression and for response to PARC, with the idea that the cellular source may link PARC to disease states in which it may be involved. Here we report that eosinophils obtained from individuals with mild eosinophilia express PARC as assessed by RT-PCR on eosinophil RNA. The eosinophil preparations were free of monocytes, a known source of PARC, and no RT-PCR product was obtained from neutrophils. Furthermore, PARC protein was detected by ELISA in the supernatants of eosinophils from seven of nine donors and in higher concentration in the supernatants of monocytes on day 1 of culture. Purified recombinant PARC activated human monocytes/macrophages kept in culture for 3-4 days but not freshly isolated monocytes. The threshold dose for Ca2+ mobilization as determined fluorometrically in indo 1-AM-labeled monocytes was 5 nM; maximal response was reached with ∼50 nM PARC. PARC was chemotactic for these cultured monocytes and caused actin polymerization determined by FITC-phalloidin binding and fluorescence-activated cell sorting analysis. In contrast, PARC activated neither neutrophils nor eosinophils. Eosinophil production of PARC, its chemotactic effect on monocytes and lymphocytes, and PARC's previously described localization to the lung suggest that this chemokine might play a role in pulmonary leukocyte trafficking.
AB - Pulmonary and activation-regulated chemokine (PARC/CCL18) belongs to the family of CC chemokines and shares 61% sequence identity with monocyte inflammatory protein (MIP)-1α. Produced by dendritic cells and macrophages primarily in the lung, PARC is known to be chemotactic for T cells. Because PARC's biological function is largely unknown, we screened various leukocyte populations for PARC expression and for response to PARC, with the idea that the cellular source may link PARC to disease states in which it may be involved. Here we report that eosinophils obtained from individuals with mild eosinophilia express PARC as assessed by RT-PCR on eosinophil RNA. The eosinophil preparations were free of monocytes, a known source of PARC, and no RT-PCR product was obtained from neutrophils. Furthermore, PARC protein was detected by ELISA in the supernatants of eosinophils from seven of nine donors and in higher concentration in the supernatants of monocytes on day 1 of culture. Purified recombinant PARC activated human monocytes/macrophages kept in culture for 3-4 days but not freshly isolated monocytes. The threshold dose for Ca2+ mobilization as determined fluorometrically in indo 1-AM-labeled monocytes was 5 nM; maximal response was reached with ∼50 nM PARC. PARC was chemotactic for these cultured monocytes and caused actin polymerization determined by FITC-phalloidin binding and fluorescence-activated cell sorting analysis. In contrast, PARC activated neither neutrophils nor eosinophils. Eosinophil production of PARC, its chemotactic effect on monocytes and lymphocytes, and PARC's previously described localization to the lung suggest that this chemokine might play a role in pulmonary leukocyte trafficking.
KW - Novel source
KW - Novel target cell
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U2 - 10.1152/ajplung.00323.2002
DO - 10.1152/ajplung.00323.2002
M3 - Article
C2 - 12716654
AN - SCOPUS:1242284514
SN - 1040-0605
VL - 286
SP - L494-L501
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 3 30-3
ER -