RESUMO
Medium conditioned by tumor necrosis factor alpha (TNF-alpha)-stimulated polymorphonuclear leukocytes (PMN) (CM-TNF) suppresses PMN migration. Therefore, we wished to identify the agent(s) in CM-TNF that mediated antichemotactic activity. CM-TNF was fractionated by high-performance liquid chromatography, and one fraction with antichemotactic activity contained the bactericidal protein human neutrophil protein 1 (HNP-1). We showed that HNP-1 suppresses PMN migration to formyl-methionyl-leucyl-phenylalanine but not to interleukin 8.
Assuntos
Quimiotaxia de Leucócito/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , alfa-Defensinas/farmacologia , Western Blotting , Cromatografia Líquida de Alta Pressão , Humanos , Técnicas In Vitro , Interleucina-8/farmacologia , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Receptores de Interleucina-8A/metabolismo , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Interleukin-8 (IL-8) is an important mediator of neutrophil (PMN) function and the type A IL-8 receptor (IL-8RA) mediates these pro-inflammatory signals. Hypoxia or hypoxia/reoxygenation (H/R) affects the production of IL-8, but no data is available regarding its effect on IL-8RA expression. The purpose of this study was to determine the effects of hypoxia and/or H/R on the expression of IL-8RA in PMN. We demonstrated that IL-8RA mRNA levels were similar under normoxic and hypoxic conditions but H/R resulted in a significant reduction in mRNA expression between 30 and 60 min. IL-8RA protein also decreased with reoxygenation of whole blood, which was altered by the addition of specific antioxidants. Therefore, H/R appears to attenuate the effect of IL-8 by down-regulating IL-8RA in PMN. These data show that changes in oxygen tension within the wound site not only affect the expression of inflammatory cytokines, but also control their actions by regulating their receptors.
Assuntos
Antígenos CD/metabolismo , Hipóxia Celular , Neutrófilos/metabolismo , Receptores de Interleucina/metabolismo , Alanina/farmacologia , Antígenos CD/efeitos dos fármacos , Antígenos CD/genética , Antioxidantes/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Dimetil Sulfóxido/farmacologia , Feminino , Humanos , Interleucina-8/metabolismo , Masculino , Neutrófilos/efeitos dos fármacos , Oxigênio/metabolismo , RNA Mensageiro/metabolismo , Receptores de Interleucina/efeitos dos fármacos , Receptores de Interleucina/genética , Receptores de Interleucina-8A , Azida Sódica/farmacologia , Superóxido Dismutase/farmacologia , Fatores de TempoRESUMO
Hemorrhage of 14 ml/kg in 5 min was done in two groups of chronically prepared, splenectomized Yorkshire pigs. Group 1 was studied on post-operative day 4 and was conditioned behaviorally with "active restraint", whereas group 2 was studied on postoperative day 6 and was conditioned with behavioral "shaping." The peak decrease in blood volume occurred by 0.25 h after hemorrhage in both groups. However, plasma atrial natriuretic factor (ANF) as measured by radioimmunoassay did not decrease significantly until 2 h in group 1 and 0.5 h in group 2 even though the recovery of blood volume was significantly more rapid in group 1 than in group 2. The responses of ANF differed significantly between groups, suggesting that ANF release after hemorrhage is influenced by prior handling and the time for recovery from surgery. In both groups, some pigs showed increases in ANF during the 1st h after hemorrhage, and changes in ANF were unrelated to decreases in central venous pressure or absolute right atrial volume determined with a conductance catheter. In contrast, changes in ANF after hemorrhage correlated positively with several variables including atrial rate and changes in vasopressin. Multiple regression suggested that the effect of reduced atrial volume on ANF release was opposed by these latter variables or related factors. Furthermore, known actions of ANF do not appear to account for the observed hemodynamic and hormonal responses to hemorrhage.
