Infusion of paniculate yeast cell wall glucan into rats results in the development of angiocentric, foreign body-type pulmonary granulomas composed almost entirely of monocytes and macrophages. Completed studies indicate that both the transient, localized accumulation of circulating neutrophils and the localized expression of monocyte chemoattractant protein-1 (MCP-1) are pivotal to subsequent granuloma formation even though few neutrophils are found in definitive lesions. We examined the role of complement as a potential modulator of MCP-1 expression and subsequent granuloma formation. Depletion of a functional complement system was carried out through, repetitive cobra venom factor infusions. There were marked reductions in mean granuloma size and number per area in complement-depleted rats compared to controls. The degree of reduction in mean granuloma size and number was related to the degree of functional complement depletion. In vitro studies confirmed that assembly of functional, sublytic concentrations of MAC on human umbilical vein endothelial cells resulted in the upregulation of MCP-1 expression. In conjunction with previous studies that suggest a pivotal role for MCP-1; these observations suggest a mechanism through which the complement system may participate in glucan-induced granuloma formation.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology