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1 Division of Cancer Biology and Vascular Biology, La Jolla Institute for Molecular Medicine, San Diego, CA, USA
2 Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA; Department of Surgery, Kumamoto University, Kumamoto, Japan
* To whom correspondence should be addressed. E-mail: ingrid{at}jimm.org.
Pulmonary and activation-regulated chemokine (PARC/CCL18) belongs to the family of CC chemokines and shares 61% sequence identity with MIP-1
. It is produced by dendritic cells and macrophages primarily in the lung and is known to be chemotactic for T-cells.
Since the biological function of PARC is largely unknown, various leukocyte populations were screened for expression of PARC as well as 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, which are 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 7 out of 9 donors and in higher concentration in the supernatants of monocytes on the first day 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, and maximal response was reached with about 50 nM PARC. PARC was chemotactic for these cultured monocytes and caused actin polymerization determined by FITC-phalloidin binding and FACS analysis. In contrast neither neutrophils nor eosinophils were activated by PARC.
The production of PARC by eosinophils, its chemotactic effect on monocytes and lymphocytes and the previously described localization of PARC to the lung suggest that this chemokine might play a role in pulmonary leukocyte trafficking.
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