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Human alveolar macrophages prevent apoptosis in polymorphonuclear leukocytes
J P Herlihy1, M W Vermeulen, C A Hales
1Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, USA.
Abstract:
Polymorphonuclear leukocytes (PMN) are recruited to the lungs to defend against injury and infection. However, PMN undergo apoptosis, thereby losing functional ability within hours, and die with lysis soon thereafter unless they receive specific signals preventing this phenomenon. We hypothesized that alveolar macrophages (AM) could provide these signals. Therefore AM, obtained through bronchoalveolar lavage of healthy volunteers (n = 9), were cultured for 24 h, after which the AM conditioned media (AM-CM) were removed. Freshly isolated PMN, which showed no apoptosis, were suspended in AM-CM, as well as in unconditioned media (UM), and followed over 48 h for apoptosis and survival. In eight of nine patients, AM-CM contained tumor necrosis factor (TNF), which modestly delayed AM apoptosis so that the percentage of PMN apoptotic at 24 h was 77 +/- 6% in AM-CM compared with 91 +/- 2% in UM (P < 0.05). In one patient, urticaria developed early in the lavage, and this subject's AM-CM profoundly prevented apoptosis of PMN (to 10% at 24 h). PMN survival in this patient was similarly enhanced, so that at 48 h of culture it was 60%, compared with 45 +/- 8% in AM-CM and 30 +/- 6% in UM (P < 0.05 UM vs. AM-CM). Granulocyte/macrophage colony-stimulating factor (GM-CSF), in addition to TNF-alpha, partly accounted for this medium's activity. Thus AM can delay apoptosis in PMN through production of TNF-alpha and in some cases by GM-CSF. When activated in vivo by conditions such as an allergic reaction, AM can rapidly and profoundly suppress PMN apoptosis.
Insights
Alveolar macrophages (AM) release factors like TNF-alpha and GM-CSF that delay programmed cell death (apoptosis) in neutrophils (PMN). Activated AM can significantly suppress PMN apoptosis, aiding lung defense.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Background:
- Polymorphonuclear leukocytes (PMN) are crucial for lung defense against pathogens and injury.
- PMN normally undergo rapid apoptosis and lysis, limiting their functional lifespan.
- Alveolar macrophages (AM) are hypothesized to provide signals that prevent PMN apoptosis.
Purpose of the Study:
- To investigate whether alveolar macrophages (AM) can prevent polymorphonuclear leukocyte (PMN) apoptosis.
- To identify factors produced by AM that influence PMN survival.
Main Methods:
- AM were isolated from healthy volunteers via bronchoalveolar lavage.
- AM-conditioned media (AM-CM) were generated.
- Freshly isolated PMN were cultured in AM-CM or unconditioned media (UM) for 48 hours.
- Apoptosis and survival rates of PMN were assessed.
Main Results:
- AM-CM from most subjects modestly delayed PMN apoptosis compared to UM.
- In one subject with urticaria, AM-CM profoundly inhibited PMN apoptosis and enhanced survival.
- Tumor necrosis factor-alpha (TNF-alpha) and granulocyte/macrophage colony-stimulating factor (GM-CSF) were identified as contributing factors.
Conclusions:
- AM produce TNF-alpha, which delays PMN apoptosis.
- In certain conditions, like allergic reactions, AM can produce GM-CSF, leading to a more profound suppression of PMN apoptosis.
- Activated AM play a significant role in regulating PMN lifespan and function in the lungs.