Eosinophils and monocytes produce pulmonary and activation-regulated chemokine, which activates cultured monocytes/macrophages

1 Divisions of Cancer Biology and Vascular Biology, La Jolla Institute for Molecular Medicine, San Diego 92121; and 2 Department of Immunology, The Scripps Research Institute, La Jolla, California 92037 Submitted 25 September 2002 ; accepted in final form 23 April 2003 Pulmonary and activation-regulated chemokine (PARC/CCL18) belongs to the family of CC chemokines and shares 61% sequence identity with monocyte inflammatory protein (MIP)-1 . 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 Ca 2+ 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. novel source; novel target cell Address for reprint requests and other correspondence: I. Schraufstatter, Div. of Cancer Biology, La Jolla Inst. for Molecular Medicine, 4570 Executive Dr., #100, San Diego, CA 92121 (E-mail: ingrid{at}ljimm.org ).