Effect of lipopolysaccharide on the morphology and integrin immunoreactivity of ramified microglia in the mouse brain and in cell culture

Microglial cells form the first line of defense in brain infection. They ar e related to monocytes and macrophages and can be readily activated by cell wall components of bacteria such as lipopolysaccharides (LPS). In the pres ent study, we explored the effect of this endotoxin in mouse on the morphol ogy of microglia and their immunoreactivity for the integrin family of cell . adhesion molecules in vitro and in vivo. Subcutaneous injection of LPS le d to a dose-dependent activation of alphaM beta2-positive microglia, with a saturating effect at 1 mug LPS in the blood-brain barrier deficient area p ostrema, at 10 mug in the directly adjacent tissue, and at 100 mug througho ut the brainstem and cerebellum. Morphologically, this activation was chara cterized by the swelling of the microglial cell body, a thickening of the p roximal processes, and a reduction in distal ramification. Microglial immun oreactivity for the integrins alpha4 beta1, alpha5 beta1, alpha6 beta1, and alphaM beta2 was strongly increased. In vitro, ramified microglia were obt ained using a coculture on top of a confluent astrocyte mono layer. Two day s exposure to LPS resulted in a morphological activation of the cultured ce lls with an increase of the integrin immunoreactivity for alpha5 (5.7-fold) , alpha4 (3.1-fold), beta1 (2.3-fold), and alphaM (1.5-fold), and a decreas e in the alpha6-staining intensity by 39%. Even a sublethal dose of LPS (3 mg in vivo and 500 mug/ml in vitro, respectively) did not induce the phagoc yte-associated integrin alphaX beta2 (CD11c/CD18, p150,95) and did not lead to a morphological transformation of the ramified microglia into phagocyte s. (C) 2001 Academic Press.