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Surfactant protein D regulates the cell surface expression of alveolar macrophage β2-integrins

Identifieur interne : 001C00 ( Main/Exploration ); précédent : 001B99; suivant : 001C01

Surfactant protein D regulates the cell surface expression of alveolar macrophage β2-integrins

Auteurs : Albert P. Senft [États-Unis] ; Thomas R. Korfhagen [États-Unis] ; Jeffrey A. Whitsett [États-Unis] ; Ann Marie Levine [États-Unis]

Source :

RBID : Pascal:07-0178860

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English descriptors

Abstract

The β2-integtin receptors (CD11a/ CD18, CD1 1b/CD18, and CD1* 1c/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 CD1 la or CD18, on alveolar macrophages. While cell surface receptors were reduced, CD11 b and CD11c c 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 β2-integrin receptors in response to changes in alveolar SP-D. Surface CD1 Ib and CD1 Ic 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 CDllc of repletion of SP-D. SP-D deficiency caused a loss of cellular CD11b and CD I 1c 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 CDllc. SP-D regulates surface CD11b and CDllc levels on the alveolar macrophage by modulating receptor trafficking, providing a mechanism by which SP-D mediates phagocytic activity in the alveolar macrophage.


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<term>Animals</term>
<term>CD11b Antigen (metabolism)</term>
<term>CD11c Antigen (metabolism)</term>
<term>Cell surface</term>
<term>Female</term>
<term>Gene Expression Regulation (drug effects)</term>
<term>Hydroxychloroquine (pharmacology)</term>
<term>Lysosomes (drug effects)</term>
<term>Lysosomes (metabolism)</term>
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<term>Pulmonary Surfactant-Associated Protein D (metabolism)</term>
<term>RNA, Messenger (genetics)</term>
<term>RNA, Messenger (metabolism)</term>
<term>Respiratory system</term>
<term>Surfactant</term>
<term>β2 integrin</term>
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<term>Hydroxychloroquine (pharmacologie)</term>
<term>Lysosomes ()</term>
<term>Lysosomes (métabolisme)</term>
<term>Macrophages alvéolaires ()</term>
<term>Macrophages alvéolaires (cytologie)</term>
<term>Macrophages alvéolaires (métabolisme)</term>
<term>Mâle</term>
<term>Protéine D associée au surfactant pulmonaire (déficit)</term>
<term>Protéine D associée au surfactant pulmonaire (métabolisme)</term>
<term>Régulation de l'expression des gènes ()</term>
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<term>Transport de protéines ()</term>
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<term>CD11c Antigen</term>
<term>Pulmonary Surfactant-Associated Protein D</term>
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<front>
<div type="abstract" xml:lang="en">The β
<sub>2</sub>
-integtin receptors (CD11a/ CD18, CD1 1b/CD18, and CD1* 1c/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 CD1 la or CD18, on alveolar macrophages. While cell surface receptors were reduced, CD11 b and CD11c c mRNAs were increased by SP-D deficiency. CCSP-rtTA
<sup>+</sup>
/(tetO)
<sub>7</sub>
-rSPD
<sup>+</sup>
/SP-D / mice, which conditionally express SP-D in the lung, were used to study the kinetics and reversibility of β
<sub>2</sub>
-integrin receptors in response to changes in alveolar SP-D. Surface CD1 Ib and CD1 Ic 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 CDllc of repletion of SP-D. SP-D deficiency caused a loss of cellular CD11b and CD I 1c 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 CDllc. SP-D regulates surface CD11b and CDllc levels on the alveolar macrophage by modulating receptor trafficking, providing a mechanism by which SP-D mediates phagocytic activity in the alveolar macrophage.</div>
</front>
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