PMID- 15596412 OWN - NLM STAT- MEDLINE DCOM- 20050215 LR - 20071115 IS - 1521-6616 (Print) IS - 1521-6616 (Linking) VI - 114 IP - 1 DP - 2005 Jan TI - Elevated monocyte chemotactic proteins 1, 2, and 3 in pulmonary alveolar proteinosis are associated with chemokine receptor suppression. PG - 79-85 AB - Pulmonary alveolar proteinosis (PAP) is a rare autoimmune lung disease characterized by abnormal surfactant accumulation within alveolar macrophages, and circulating auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) resulting in functional GM-CSF deficiency. Monocyte/macrophage chemotactic protein-1 (MCP-1) is elevated in PAP, suggesting association with the pathophysiology. Because PAP has been associated with inflammatory pulmonary changes, we hypothesized that other MCP family chemokines would be present and that Chemokine Chemotaxis Receptor 2 (CCR2) would be elevated on PAP mononuclear cells. Here we show for the first time that MCP-2 and MCP-3, like MCP-1, are highly elevated in PAP. We also confirm that PAP alveolar macrophages and not epithelial cells produce MCP-1, and that MCP-1 from PAP lung has functional chemoattractant activity. Surprisingly, CCR2 expression is diminished in PAP lymphocytes and alveolar macrophages compared to controls. Further, MCP-1 from PAP lung suppresses CCR2 expression in vitro, suggesting that in PAP, MCP-1 participates in an autocrine regulatory network in vivo. FAU - Bonfield, Tracey L AU - Bonfield TL AD - Department of Pulmonary, Allergy and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. FAU - John, Nejimol AU - John N FAU - Malur, Anagha AU - Malur A FAU - Barna, Barbara P AU - Barna BP FAU - Culver, Daniel A AU - Culver DA FAU - Kavuru, Mani S AU - Kavuru MS FAU - Thomassen, Mary Jane AU - Thomassen MJ LA - eng PT - Journal Article PL - United States TA - Clin Immunol JT - Clinical immunology (Orlando, Fla.) JID - 100883537 RN - 0 (CCL7 protein, human) RN - 0 (CCL8 protein, human) RN - 0 (CCR2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL7) RN - 0 (Chemokine CCL8) RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (Monocyte Chemoattractant Proteins) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) SB - IM MH - Adult MH - Aged MH - Bronchoalveolar Lavage MH - Chemokine CCL2/*metabolism MH - Chemokine CCL7 MH - Chemokine CCL8 MH - Chemokines/physiology MH - Cytokines/*metabolism MH - Down-Regulation MH - Female MH - Gene Expression MH - Humans MH - Macrophages, Alveolar/immunology MH - Male MH - Middle Aged MH - Monocyte Chemoattractant Proteins/*metabolism MH - Pulmonary Alveolar Proteinosis/*immunology MH - Receptors, CCR2 MH - Receptors, Chemokine/biosynthesis/*physiology EDAT- 2004/12/15 09:00 MHDA- 2005/02/16 09:00 CRDT- 2004/12/15 09:00 PHST- 2004/08/04 00:00 [received] PHST- 2004/09/13 00:00 [accepted] PHST- 2004/12/15 09:00 [pubmed] PHST- 2005/02/16 09:00 [medline] PHST- 2004/12/15 09:00 [entrez] AID - S1521-6616(04)00290-6 [pii] AID - 10.1016/j.clim.2004.09.004 [doi] PST - ppublish SO - Clin Immunol. 2005 Jan;114(1):79-85. doi: 10.1016/j.clim.2004.09.004.