Macrophages in muscle layer of gastrointestinal tract: Impairment of muscle contraction by treatment with lipopolysaccharide

The morphology and function of resident macrophages in the muscle layer and in the subserosa of the gastrointestinal tract are described. FITC-dextran injected via the tail vein of a mouse or rat demonstrated a regular arrang ement of macrophages on a whole mount preparation of the muscle layer. Elec tron microscopy revealed inactive phagocytosis under normal conditions. Aft er a 4-8 hr incubation of rat ileal muscle with lipopolysaccharide (LPS) to investigate its effect on muscle contraction, macrophages began to express inducible nitric oxide synthase (iNOS) and released nitric oxide. This mac rophage response was accompanied by the expression of cyclooxygenase-2 (COX -2) immunoreactivity and the production of prostaglandins. The muscarinic a gonist-induced contraction was greatly inhibited by LIPS treatment, and thi s inhibition was reversed by either iNOS or COX-2 inhibitors. We concluded that one of the functions of muscular macrophages was the modulation of smo oth muscle contraction under pathological conditions. The mechanism of iNOS upregulation indicated by our experiment is discussed.