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 chemokines, which exhibits, in addition to proinflammatory activities, a potent endogenous pyrogen activity. In this study, we analysed the time-course of expression and cellular source of macrophage inflammatory protein-1alpha and macrophage inflammatory protein-1beta, in inflammation of the rat brain associated with ischemia and endotoxemia. Using in situ hybridization histochemistry, we observed that intravenously injected bacterial lipopolysaccharide induced a transient expression of macrophage inflammatory protein-1alpha and macrophage inflammatory protein-1beta messenger RNAs throughout the brain, with maximal expression 8-12 h after lipopolysaccharide treatment. We also revealed an early increase in macrophage inflammatory protein-1alpha and macrophage inflammatory protein-1beta messenger RNA levels, after permanent 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 middle cerebral artery occlusion. The induction of macrophage inflammatory protein-1 messenger RNA was clearly stronger in the transient than in the permanent middle cerebral artery-occluded rat brains, showing that the reperfusion process influences the extent of the chemokine response after middle cerebral artery occlusion. In situ hybridization combined with immunohistochemistry for glial fibrillary acidic protein, a specific marker for astrocytes, excluded astrocytes as the cellular source of macrophage inflammatory protein-1 messenger RNAs after both middle cerebral artery ischemia and lipopolysaccharide treatment. Using immunohistochemistry, macrophage inflammatory protein-1alpha protein expression was shown to be induced in a time-dependent manner after lipopolysaccharide treatment and middle cerebral artery occlusion. Macrophage inflammatory protein-1alpha immunopositive cells co-localized 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 infection, and might modulate the host defence febrile response to a pathogenic stimulus.