PRODUCTION OF ANGIOGENIC ACTIVITY BY HUMAN MONOCYTES REQUIRES AN L-ARGININE NITRIC-OXIDE SYNTHASE-DEPENDENT EFFECTOR MECHANISM

被引:190
作者
LEIBOVICH, SJ
POLVERINI, PJ
FONG, TW
HARLOW, LA
KOCH, AE
机构
[1] NORTHWESTERN UNIV, SCH DENT, DEPT PATHOL, CHICAGO, IL 60611 USA
[2] NORTHWESTERN UNIV, SCH DENT, DEPT BASIC SCI, CHICAGO, IL 60611 USA
[3] NORTHWESTERN UNIV, SCH MED, DEPT MED, CHICAGO, IL 60611 USA
关键词
MACROPHAGE; STIMULATION; ENDOTHELIUM; CYTOKINES; CHEMOTAXIS;
D O I
10.1073/pnas.91.10.4190
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Human monocytes (M phi) require stimulation with substances such as bacterial endotoxin [LPS (lipopolysaccharide)] to produce angiogenic activity. In this study, we report that stimulation of M phi with LPS (5 mu g/ml) in the absence of L-arginine greatly reduced their production of angiogenic activity, as assessed in vivo in rat corneas and in vitro by chemotaxis of human umbilical vein endothelial cells (HU-VECs). D-Arginine did not substitute for L-arginine in the production of angiogenic activity. The nitric oxide synthase (NO synthase, EC 1.14.13.39) inhibitors N-G-monomethyl-L-arginine (L-NMMA) and N-G-nitro-L-arginine methyl ester (L-NAME) both inhibited the production of angiogenic activity by LPS-stimulated M phi in the presence of L-arginine, suggesting the involvement of this enzyme in the pathway that generates angiogenic activity. Neither of these substances directly inhibited the M phi-derived angiogenic activity. LPS-induced production of the cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 8 (IL-8) was not significantly reduced when M phi were incubated in the absence of L-arginine. Similarly, L-NMMA and L-NAME did not significantly reduce the LPS-induced production of these cytokines by M phi in the presence of L-arginine. These results suggest that the LPS-stimulation-dependent generation of angiogenic activity by M phi requires an L-arginine-dependent NO-synthase effector mechanism that may be independent of the generation of TNF-alpha and IL-8.
引用
收藏
页码:4190 / 4194
页数:5
相关论文
共 46 条
[1]   THE CELL BIOLOGY OF MACROPHAGE ACTIVATION [J].
ADAMS, DO ;
HAMILTON, TA .
ANNUAL REVIEW OF IMMUNOLOGY, 1984, 2 :283-318
[2]   A RAPID METHOD FOR THE ASSAY OF NITRATE IN URINE USING THE NITRATE REDUCTASE ENZYME OF ESCHERICHIA-COLI [J].
BARTHOLOMEW, B .
FOOD AND CHEMICAL TOXICOLOGY, 1984, 22 (07) :541-543
[3]  
EFRON DT, 1991, SURGERY, V110, P327
[4]   TUMOR-NECROSIS-FACTOR TYPE-ALPHA, A POTENT INHIBITOR OF ENDOTHELIAL-CELL GROWTH-INVITRO, IS ANGIOGENIC INVIVO [J].
FRATERSCHRODER, M ;
RISAU, W ;
HALLMANN, R ;
GAUTSCHI, P ;
BOHLEN, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (15) :5277-5281
[5]  
GARTHWAITE G, 1991, TRENDS NEUROSCI, V2, P60
[6]   A SPECTROPHOTOMETRIC ASSAY FOR NITRATE USING NADPH OXIDATION BY ASPERGILLUS NITRATE REDUCTASE [J].
GILLIAM, MB ;
SHERMAN, MP ;
GRISCAVAGE, JM ;
IGNARRO, LJ .
ANALYTICAL BIOCHEMISTRY, 1993, 212 (02) :359-365
[7]   TUMOR-GROWTH AND NEOVASCULARIZATION - EXPERIMENTAL MODEL USING RABBIT CORNEA [J].
GIMBRONE, MA ;
COTRAN, RS ;
LEAPMAN, SB ;
FOLKMAN, J .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1974, 52 (02) :413-427
[8]   A TUMOR SUPPRESSOR-DEPENDENT INHIBITOR OF ANGIOGENESIS IS IMMUNOLOGICALLY AND FUNCTIONALLY INDISTINGUISHABLE FROM A FRAGMENT OF THROMBOSPONDIN [J].
GOOD, DJ ;
POLVERINI, PJ ;
RASTINEJAD, F ;
LEBEAU, MM ;
LEMONS, RS ;
FRAZIER, WA ;
BOUCK, NP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (17) :6624-6628
[9]   ANALYSIS OF NITRATE, NITRITE, AND [N-15]-LABELED NITRATE IN BIOLOGICAL-FLUIDS [J].
GREEN, LC ;
WAGNER, DA ;
GLOGOWSKI, J ;
SKIPPER, PL ;
WISHNOK, JS ;
TANNENBAUM, SR .
ANALYTICAL BIOCHEMISTRY, 1982, 126 (01) :131-138
[10]  
HASKILL S, 1988, J IMMUNOL, V140, P1690