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This Article Full Text Full Text (PDF) All Versions of this Article: 292/2/L469    most recent 00297.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Senft, A. P. Articles by LeVine, A. M. Search for Related Content PubMed PubMed Citation Articles by Senft, A. P. Articles by LeVine, A. M.

Surfactant protein D regulates the cell surface expression of alveolar macrophage ₂-integrins

¹Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; and ²Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida

Submitted 7 August 2006 ; accepted in final form 17 October 2006

The ₂-integrin receptors (CD11a/CD18, CD11b/CD18, and CD11c/CD18) are expressed on the surface of alveolar macrophages and are important for the phagocytic clearance of pathogens. In the present study, we demonstrate that surfactant protein D (SP-D) modulates surface expression of CD11b and CD11c, but not CD11a or CD18, on alveolar macrophages. While cell surface receptors were reduced, CD11b and CD11c mRNAs were increased by SP-D deficiency. CCSP-rtTA⁺/(tetO)₇-rSPD⁺/SP-D^–/– mice, which conditionally express SP-D in the lung, were used to study the kinetics and reversibility of ₂-integrin receptors in response to changes in alveolar SP-D. Surface CD11b and CD11c were reduced on the alveolar macrophages within 3 days of SP-D deficiency and were restored with 3 days for CD11b and 7 days for CD11c of repletion of SP-D. SP-D deficiency caused a loss of cellular CD11b and CD11c content, indicating that the decrease in total cell content of the receptors was related to degradation rather than to redistribution of the receptor within the macrophage. CD11b and CD11c staining colocalized with Lamp-1 during SP-D deficiency, supporting the concept that reduced macrophage receptor levels resulted from increased lysosomal trafficking. Hydroxychloroquine, a lysomotropic agent, prevented the reduction of cellular and surface CD11b and CD11c. SP-D regulates surface CD11b and CD11c levels on the alveolar macrophage by modulating receptor trafficking, providing a mechanism by which SP-D mediates phagocytic activity in the alveolar macrophage.