Surfactant protein D regulates the cell surface expression of alveolar macrophage beta(2)-integrins.
The beta(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 beta(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.
Senft
Albert P
AP
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Korfhagen
Thomas R
TR
Whitsett
Jeffrey A
JA
LeVine
Ann Marie
AM
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism*; D039521:CD11c Antigen / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006886:Hydroxychloroquine / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D021381:Protein Transport / Q000187:drug effects; D037663:Pulmonary Surfactant-Associated Protein D / Q000172:deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D039481:CD11b Antigen; D039521:CD11c Antigen; D037663:Pulmonary Surfactant-Associated Protein D; D012333:RNA, Messenger; D006886:Hydroxychloroquine