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Assessment of neonatal avian inflammatory macrophage function following embryonic cyclophosphamide exposure
K A Golemboski1, S E Bloom, R R Dietert
1Department of Microbiology, Immunology and Parasitology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
Insights
Embryonic cyclophosphamide (CP) exposure in chickens impairs bursa and testes growth but does not affect inflammatory macrophage function. This suggests avian inflammatory macrophages recover function despite early-life immune system damage.
Area of Science:
- Immunology
- Developmental Biology
- Avian Biology
Background:
- Cyclophosphamide (CP) is an immunosuppressive drug used in research.
- Embryonic exposure to CP can cause significant immune system damage.
- Understanding long-term effects on immune cells like macrophages is crucial.
Purpose of the Study:
- To investigate the long-term effects of embryonic cyclophosphamide (CP) exposure on avian inflammatory macrophage function.
- To assess if CP-induced bursal damage impacts macrophage recruitment and activity in chickens.
Main Methods:
- Chickens received two doses of cyclophosphamide (CP) or vehicle during late embryogenesis.
- Mononuclear leukocyte chemotaxis to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was assessed.
- Peritoneal exudate cells (PECs) were analyzed for cell number, type, superoxide anion production, and surface antigen expression (Ia, TfR).
- Hematological parameters and organ weights (bursa, testes) were measured.
Main Results:
- CP-treated chickens showed reduced bursa weight and inhibited testes growth in males.
- No significant differences were observed in mononuclear leukocyte chemotaxis or hematological parameters.
- Peritoneal exudate cells from CP-treated chickens did not differ in cell number, type, superoxide production, or Ia/TfR expression compared to controls.
- Despite bursal damage and impaired humoral immunity, macrophage function remained unaffected.
Conclusions:
- Embryonic cyclophosphamide (CP) exposure in chickens leads to irreversible bursal damage and impaired humoral immunity.
- Inflammatory macrophage recruitment and function are not permanently affected by this early-life immunosuppression.
- Avian inflammatory macrophages exhibit resilience and functional recovery following embryonic CP exposure.
Abstract:
Inflammatory macrophage recruitment and function were examined in 4-5-week-old chickens which had received two doses of cyclophosphamide (CP) or vehicle (dH2O) during late embryogenesis (18 and 19 days of incubation). Mononuclear leukocyte chemotaxis to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and hematological parameters were unchanged in CP-treated vs control chickens. Peritoneal exudate cells (PECs) elicited in response to intraperitoneal (i.p.). Sephadex injection did not differ in CP-treated vs control chickens with respect to cell number, cell type, superoxide anion production, or cell surface expression of Ia and transferrin receptor (TfR) antigens. The CP-treated chickens did exhibit the expected decrease in bursa weight; male chickens exposed to CP also had inhibited testes growth. Although embryonic exposure to CP at this dose results in irreversible bursal damage and subsequent impaired humoral immunity, it appears that there are no long-lasting effects on avian inflammatory macrophage function.