Effects of CNI-1493 on human granulocyte functions.
During acute bacterial infections such as sepsis and meningitis, activation of inflammatory mediators such as nitric oxide (NO) plays a crucial role in both pathogenesis and host defense. We have previously reported that CNI-1493, a macrophage deactivator, reduced mortality in infant rats infected with Haemophilus influenzae type b (Hib) with associated decrease in the number of granulocytes in the infected tissue. The aim of the present study was to investigate how CNI-1493 affects granulocytes and macrophages in vitro. Murine macrophages (RAW 264.7) pre-incubated with CNI-1493 prior to activation with lipopolysaccharide (LPS)/interferon gamma (IFNgamma) had decreased NO production measured as NO(2)(-)/NO(3)(-) levels and reduction in inducible NO-synthase (iNOS) expression. Reactive oxygen species (ROS) production was increased in formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated granulocytes following CNI-1493 treatment, whereas F-actin content, motility and chemotaxis were decreased under the same conditions. The effects of CNI-1493 on both NO production in LPS/IFNgamma-activated macrophages and ROS production, F-actin content, motility and chemotaxis in granulocytes, may contribute to the reduced inflammatory response and increased survival in Hib-infected animals treated with CNI-1493.
Abdalla
Hana
H
Department of Molecular and Clinical Medicine, Division of Medical Microbiology, Faculty of Health Sciences, Linköping University, S-581 85 Linköping, Sweden. hanab@imk.liu.se
Forslund
Tony
T
Schön
Thomas
T
Stendahl
Olle
O
Sundqvist
Tommy
T
D000199:Actins / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D002464:Cell Migration Inhibition / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D006098:Granulocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D000813:Anilides; D006146:Guanidines
D000199:Actins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006835:Hydrazones; D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D017382:Reactive Oxygen Species; C097256:semapimod; D000813:Anilides; D006146:Guanidines