Monocyte-vascular smooth muscle cell interaction enhances nitric oxide production

doi:10.1016/S0008-6363(97)00265-4

Cardiovascular Research 1998 37(3):820-825; doi:10.1016/S0008-6363(97)00265-4
© 1998 by European Society of Cardiology

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Monocyte–vascular smooth muscle cell interaction enhances nitric oxide production

Uichi Ikeda^a^,*, Yoshikazu Maeda^a, Hiroshi Funayama^a, Yukihiro Hojo^a, Michiyo Ikeda^b, Seiji Minota^b, Shogo Kano^b and Kazuyuki Shimada^a

^aDepartment of Cardiology, Jichi Medical School, Tochigi, Japan
^bDepartment of Clinical Immunology, Jichi Medical School, Tochigi, Japan

^* Corresponding author. Department of Cardiology, Jichi Medical School, Minamikawachi-machi, Tochigi 329-04, Japan. Tel. (+81-285) 44-2111, ext. 3556; Fax (+81-285) 44-5317; E-mail: uikeda@jichi.ac.jp

Objective: The adhesive interaction of monocytes and vascularsmooth muscle cells (VSMCs) has been suggested to be a regulatorysignal in the cellular activation that is involved in the pathogenesisof atherosclerosis. We investigated the effects of monocyte–VSMCinteraction on inducible nitric oxide (NO) synthase expression.Methods: NO production by the cultured cells was determinedby measuring the nitrite content of the culture media usingthe Griess reagent. The expression of inducible NO synthaseprotein was assayed by Western blotting. Results: Interleukin-1β(IL-1β) induced nitrite production by VSMCs in a time-dependentmanner. The addition of the mouse monocyte cell line J774 toIL-1β-stimulated VSMCs further increased nitrite productionin a monocyte number-dependent manner. Enhanced nitrite productionby coculture was accompanied by increased inducible NO synthaseprotein accumulation. Addition of tumor necrosis factor- ${alpha}$ (TNF- ${alpha}$ )also enhanced IL-1β-induced nitrite production by VSMCs,but TNF- ${alpha}$ showed no effect in the presence of monocytes. Cocultureof monocytes and VSMCs in the presence of IL-1β secretedsubstantial amounts of TNF- ${alpha}$ . The production of nitrite by coculturewas markedly inhibited by an anti-TNF- ${alpha}$ antibody. Conclusions:The present study revealed that direct cell-to-cell interactionbetween monocytes and VSMCs enhances NO production, suggestingan important role for their interaction in the pathogenesisof atherosclerosis.

KEYWORDS Monocyte; Vascular smooth muscle; Nitrite; Atherosclerosis

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