Smoker's Lung Transplanted to a Nonsmoker

Abstract

Alveolar macrophages (AM) from smokers contain characteristic smoker's inclusion bodies within the cytoplasm as a result of ingestion of substances in the inhaled smoke. How long these smoking-related changes in the AM population can be seen after smoking cessation is largely unknown. We had the unique opportunity to investigate a 51-yr-old never-smoker after single lung transplantation (TX) for alpha 1-antitrypsin deficiency emphysema who received a donor's lung from a heavy cigarette smoker. Serial bronchoalveolar lavage (BAL) was performed in the donor's lung for transplant surveillance at defined time intervals, and the percentage of AM with characteristic smoker's inclusions was counted on slides stained with May-Grünwald-Giemsa stain. The patient had an uneventful course after TX with no major infectious complications or episodes of rejection. One month after TX the percentage of smoker's AM was 98%. BAL after 2, 5, 7, and 12 mo showed a similar high percentage. After 18 mo a first a decrease was seen, down to 78%, and after 2 yr a decrease to 59% was seen. After 3 yr, the smoker's AM had mostly disappeared, only 3% were still present. In conclusion, smoker's inclusions in AM may be detected for at least 2 yr after smoking has ceased, which is considerably longer than the estimated life span of the AM.

Macrophages Survive Hyperoxia via Prolonged ERK Activation Due to Phosphatase Down-regulation

“…Under conditions of supplemental oxygen exposure (acutely ill patients), macrophages can be exposed to up to 90% oxygen. It is known that macrophages exposed to one type of oxidant stress, cigarette smoke, survive for prolonged periods of time in the lung (10). The prolonged life of the macrophages of smokers compared with our previous observations on the cell cycle effects of hyperoxia (hyperoxia induces macrophage cell cycle arrest accompanied by induction of p21 Cip1 and activation of the retinoblastoma protein (11)) suggests the activation of one or more survival pathways by hyperoxia.…”

Identification of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease

“…It is known that pulmonary macrophages may persist for many years within the lung, since donor macrophages can be detected 2-3 years following transplant 36 ; however, specific identification of these long-lived, resident cells in an individual that has not undergone transplant is difficult. Rodent studies of pulmonary macrophage depletion suggest that Chana 16 macrophages repopulate the lung rapidly 37,38 and this turnover is increased following infection 39 .…”

Reduced Number and Morphofunctional Change of Alveolar Macrophages in MafB Gene-Targeted Mice

“…In COPD patients, programmed cell death is observed in various cells and influences the viability of cells in the lung [23–25]. However, the AMs of smokers reportedly survive longer than those of non-smokers [26,27]. We previously demonstrated that over-expression of MafB enhanced cell viability following treatment with CSE as well as significantly inhibiting caspase-3 activity and reducing macrophage apoptosis [6].…”