Elevated monocyte chemotactic proteins 1, 2, and 3 in pulmonary alveolar proteinosis are associated with chemokine receptor suppression.
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.
Bonfield
Tracey L
TL
Department of Pulmonary, Allergy and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
John
Nejimol
N
Malur
Anagha
A
Barna
Barbara P
BP
Culver
Daniel A
DA
Kavuru
Mani S
MS
Thomassen
Mary Jane
MJ
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*
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