A Light and Electron Microscopic Study on the Role of Granulocyte Colony Stimulating Factor Therapy on Carbon Tetrachloride Induced Lung Fibrosis in Adult Male Albino Rats.

Abstract

Background: Pulmonary fibrosis is a serious fatal form of interstitial lung diseases and unfortunately no effective therapy exists. Hematopoietic Stem Cells (HSCs) have been used for hematological reconstitution for many years. Recently, however, homing and engraftment of HSCs in damaged non-hematopoietic organs have been observed and were suggested to contribute to the wound healing process. Aim of the work: To test whether the chemokine Granulocyte Colony Stimulating Factor (G-CSF) could promote lung repair and recovery after fibrosis in adult male rats. Materials and Methods: A total of eighty adult male rats were divided randomly into four groups: Group (I): Control group. Group (II): Carbon tertrachloride-treated group where the animals were injected with carbon tertrachloride (CCL4) intaperitoneally at a dose of 0.6 mg /Kg B.W daily for 14 consecutive days and then were subdivided into two subgroups: Group (a) in which the animals were sacrificed 24 hours after the last administration and Group (b) in which the animals were sacrificed 14 days after the last administration. Group (III): G-CSF+carbon tertrachloride-treated group where the animals were injected with carbon tertrachloride (CCL4) intaperitoneally at a dose of 0.6 mg /Kg B.W daily for 14 consecutive days and then G-CSF (Neupogen) in a dose of (100 μg/kg/day) subcutaneously for 5 consecutive days and the animals were sacrificed 14 days after the last administration. Group (IV): G-CSF-treated group where the animals were injected with G-CSF (Neupogen) in a dose of (100 μg/kg/day) subcutaneously for 5 consecutive days and the animals were sacrificed 14 days after the last administration. The lungs were prepared and processed for light and electron microscopic examination. Results: It has been found that rats treated with carbon tetrachloride showed extensive congestion and rupture of most of the blood capillaries, marked thickening of the interalveolar septa, marked narrowing, distortion and occlusion in most of the air spaces. A large number of inflammatory cells in the pulmonary tissue and marked increase in the amount of collagen fibers were also observed . The results obtained from the group of rats treated with both G-CSF+carbon tertrachloride revealed marked reduction in the above mentioned pathological changes in the lungs. Conclusion: Although the exact mechanisms are not wholly understood, there is evidence that bone marrow-derived stem cells are able to contribute to promote healing of lung fibrosis.