Cyclophosphamide가 흰쥐 골수의 기질세포에서 Laminin-1의 발현에 미치는 영향
Laminin-1 Expression in Bone Marrow Stromal Cells in Cyclophosphamide-treated Rat
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골수내 정상적인 혈구형성은 줄기세포와 주위의 미세환경 (microenvironment) 사이에 일어나는 상호작용에 의해서 좌우된다고 알려져 있다. 이때 미세환경은 성장요소, 기질세포 및 기질세포가 분비한 세포외기질의 복잡한 망상구조로 이루어져 있다. 골수의 세포외기질 (extracellular matrix, ECM)은 거대분자로 구성되어 있으며 이중 구성요소의 일부인 당단백이 혈구형성의 조절에 주요한 요소가 된다고 많은 학자들이 주장해 왔다.골수의 기질 (stroma)을 이루고 있는 망상세포, 지방세포, 섬유모세포, 혈관내피세포 및 혈관주위세포등이 분비하는 세포외기질에 여러종류의 laminin 동형체가 함유되어 있으며 여러 종류의 혈구형성에 주요한 역할을 한다는 연구보고가 있다.
Abstract
The purpose of the present study is to investigate whether stromal cells supporting specific microenvironment for hematopoiesis of bone marrow are affected by toxicants and therapeutic drugs such as antibiotics and anticancer drugs and whether laminin-1 is associated with such effects. SD rats were intraperitoneally injected with 75 mg/kg of cyclophosphamide which is widely used to treat infant's solid tumor, leukemia and myeloma and sacrificed after 3 days, 1 week, 3 weeks or 5 weeks of injection. The bone marrow extracted and paraffin-sectioned was analyzed using immunohistochemical staining. A part of tissues was subjected to electron microscopy following reaction with rabbit anti-laminin antibody, biotinylated goat anti-rabbit IgG conjugated with 12 mm gold particles, and staining with uranyl acetate. 1. The bone marrow tissue at day 3 post injection with cyclophosphamide displayed dilated venous sinus, partial necrotic death, and decreased number of hematopoietic cells. Laminin-1 was intensively stained in the reticular and adipose tissues.2. Up to 5 weeks post injection, laminin-1 was stained at a low level in the stromal tissue of bone marrow and the number of hematopoietic cell was increased.3. Deposition of the gold particle which represents laminin-1 expression was observed at the highest level in the stromal cells of bone marrow obtained 3 days after injection, and decreased after 1 to 5 weeks.These results suggest that stromal cells which play a role in supporting microenvironment for bone marrow hematopoiesis augment induction of laminin-1 expression and activation upon administration of cyclophosphamide.