Localization of macrophage inflammatory protein: Macrophage inflammatory PROTEIN-1 expression in rat brain after peripheral administration of lipopolysaccharide and focal cerebral ischemia

Macrophage inflammatory protein is a member of the C-C subfamily of chemoki nes, which exhibits, in addition to proinflammatory activities, a potent en dogenous pyrogen activity. In this study, we analysed the time-course of ex pression and cellular source of macrophage inflammatory protein-1 alpha and macrophage inflammatory protein-1 beta, in inflammation of the rat brain a ssociated with ischemia and endotoxemia. Using in situ hybridization histoc hemistry, we observed that intravenously injected bacterial lipopolysacchar ide induced a transient expression of macrophage inflammatory prolein-1 alp ha and macrophage inflammatory protein-1 beta messenger RNAs throughout the brain, with maximal expression 8-12 h after lipopolysaccharide treatment. We also revealed an early increase in macrophage inflammatory protein-1 alp ha and macrophage inflammatory protein-1 beta messenger RNA levels, after p ermanent and transient middle cerebral artery occlusion, starting as early as 1 h after the occlusion and reaching a peak of expression 8-16 h after m iddle cerebral artery occlusion. The induction of macrophage inflammatory p rotein-1 messenger RNA was clearly stronger in the transient than in the pe rmanent middle cerebral artery-occluded rat brains, showing that the reperf usion process influences the extent of the chemokine response after middle cerebral artery occlusion. In situ hybridization combined with immunohistoc hemistry for glial fibrillary acidic protein, a specific marker for astrocy tes, excluded astrocytes as the cellular source of macrophage inflammatory protein-1 messenger RNAs after both middle cerebral artery ischemia and lip opolysaccharide treatment. Using immunohistochemistry, macrophage inflammat ory protein-la protein expression was shown to be induced in a time-depende nt manner after lipopolysaccharide treatment and middle cerebral artery occ lusion. Macrophage inflammatory protein-lu immunopositive cells co-localize d with cells stained with OX-42 antibody, a microglia/macrophage marker. These results indicate that macrophage inflammatory protein-1 is implicated in the inflammatory reaction of the brain in response to ischemia or infec tion, and might modulate the host defence febrile response to a pathogenic stimulus. (C) 1998 IBRO. Published by Elsevier Science Ltd.