Cigarette smoke-induced changes to alveolar macrophage phenotype and function are improved by treatment with procysteine

Hodge, Sandra, Matthews, Geoffrey, Mukaro, Violet, Ahern, Jessica, Shivam, Aruna, Hodge, Greg, Holmes, Mark, Jersmann, Hubertus and Reynolds, Paul N. 2011, Cigarette smoke-induced changes to alveolar macrophage phenotype and function are improved by treatment with procysteine, American journal of respiratory cell and molecular biology, vol. 44, no. 5, pp. 673-681, doi: 10.1165/rcmb.2009-0459OC.

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Title Cigarette smoke-induced changes to alveolar macrophage phenotype and function are improved by treatment with procysteine
Author(s) Hodge, Sandra
Matthews, Geoffrey
Mukaro, Violet
Ahern, Jessica
Shivam, Aruna
Hodge, Greg
Holmes, Mark
Jersmann, Hubertus
Reynolds, Paul N.
Journal name American journal of respiratory cell and molecular biology
Volume number 44
Issue number 5
Start page 673
End page 681
Total pages 9
Publisher American Lung Association
Place of publication New York, N.Y.
Publication date 2011
ISSN 1044-1549
Keyword(s) COPD
macrophage phenotype and function
cigarette smoke
Summary Defective efferocytosis may perpetuate inflammation in smokers with or without chronic obstructive pulmonary disease (COPD). Macrophages may phenotypically polarize to classically activated M1 (proinflammatory; regulation of antigen presentation) or alternatively activated M2 (poor antigen presentation; improved efferocytosis) markers. In bronchoalveolar lavage (BAL)–derived macrophages from control subjects and smoker/ex-smoker COPD subjects, we investigated M1 markers (antigen-presenting major histocompatibility complex [MHC] Classes I and II), complement receptors (CRs), the high-affinity Fc receptor involved with immunoglobulin binding for phagocytosis (Fc-gamma receptor, FcγR1), M2 markers (dendritic cell–specific intercellular adhesion molecule-grabbing nonintegrin [DC-SIGN] and arginase), and macrophage function (efferocytosis and proinflammatory cytokine production in response to LPS). The availability of glutathione (GSH) in BAL was assessed, because GSH is essential for both M1 function and efferocytosis. We used a murine model to investigate macrophage phenotype/function further in response to cigarette smoke. In lung tissue (disaggregated) and BAL, we investigated CRs, the available GSH, arginase, and efferocytosis. We further investigated the therapeutic effects of an oral administration of a GSH precursor, cysteine l-2-oxothiazolidine-4-carboxylic acid (procysteine). Significantly decreased efferocytosis, available GSH, and M1 antigen–presenting molecules were evident in both COPD groups, with increased DC-SIGN and production of proinflammatory cytokines. Increased CR-3 was evident in the current-smoker COPD group. In smoke-exposed mice, we found decreased efferocytosis (BAL and tissue) and available GSH, and increased arginase, CR-3, and CR-4. Treatment with procysteine significantly increased GSH, efferocytosis (BAL: control group, 26.2%; smoke-exposed group, 17.66%; procysteine + smoke-exposed group, 27.8%; tissue: control group, 35.9%; smoke-exposed group, 21.6%; procysteine + smoke-exposed group, 34.5%), and decreased CR-4 in lung tissue. Macrophages in COPD are of a mixed phenotype and function. The increased efferocytosis and availability of GSH in response to procysteine indicates that this treatment may be useful as adjunct therapy for improving macrophage function in COPD and in susceptible smokers.
Language eng
DOI 10.1165/rcmb.2009-0459OC
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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