title: Elevated monocyte chemotactic proteins 1, 2, and 3 in pulmonary alveolar proteinosis are associated with chemokine receptor suppression.
abstract: 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.
authors.affiliation: Department of Pulmonary, Allergy and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Bonfield
authors.forename: Nejimol
authors.initials: N
authors.lastname: John
authors.forename: Anagha
authors.initials: A
authors.lastname: Malur
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Barna
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Culver
authors.forename: Mani S
authors.initials: MS
authors.lastname: Kavuru
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Thomassen
mesh_terms: D000328:Adult; D000368:Aged; D018893:Bronchoalveolar Lavage; D018932:Chemokine CCL2 / Q000378:metabolism*; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D018925:Chemokines / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism*; D011649:Pulmonary Alveolar Proteinosis / Q000276:immunology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000502:physiology*
chemical_list: C515450:CCL7 protein, human; C515453:CCL8 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D018925:Chemokines; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D054390:Receptors, CCR2; D019707:Receptors, Chemokine