STIMULUS AND CELL-SPECIFIC EXPRESSION OF C-X-C AND C-C CHEMOKINES BY PULMONARY STROMAL CELL-POPULATIONS

Chronic inflammatory responses in the lung rely on the continual recru itment of leukocytes to the site of inflammation. Recent data have dem onstrated a possible role for stromal cell-derived chemokines in leuko cyte recruitment. In the present study we examined the production of i nterleukin (IL)-8 and ENA-78, members of the C-X-C family of chemokine s, and macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, m embers of the C-C chemokine family, from pulmonary smooth muscle and e ndothelial cells. The production of IL-8 and ENA-78 was induced by ear ly response cytokines, IL-1 and tumor necrosis factor (TNF), but not b y immune-associated cytokines, IL-4, IL-10, or interferon (IFN)-gamma. In contrast, the production of MIP-1 alpha and MIP-1 beta by pulmonar y vascular smooth muscle cells increased when stimulated by immune-ass ociated cytokines as well as with IL-1 beta and TNF. The level of MIP- 1 alpha production induced in smooth muscle cells by the immune-associ ated cytokines, IL-4, IFN-gamma, and IL-10 ranged from 0 to 340 pg/ml. The production of MIP-1 beta in response to the immune-associated cyt okines IL-4, IFN-gamma, and IL-10 in smooth muscle cells ranged from 2 60 to 940 pg/ml. Human pulmonary artery endothelial cells did not gene rate MIP-1 alpha or MIP-1 beta in response to graded doses of any of t he cytokines. These data demonstrate differential induction of C-X-C a nd C-C chemokines from nonimmune stromal cell populations. The C-X-C c hemokines are induced primarily by early response cytokines, i.e., IL- 1 beta and TNF. However, the C-C chemokines were induced in smooth mus cle cells, but not endothelial cells, by both early response and immun e-associated cytokine stimulation. These mechanisms may be pertinent i n the development and regulation of acute and chronic inflammatory res ponses.